Search

Decades of research have investigated the mechanisms that lead to the origin of cancer, striving to identify tumor-initiating cells. These cells, also known as cancer stem cells, are characterized by the ability to self-renew, to give rise to differentiated tumor populations, and on a larger scale, are deemed responsible not only for tumor initiation but also for recurrent tumors, often resistant to chemotherapy and radiotherapy. Long noncoding RNAs are RNA molecules longer than 200 nt, lacking the ability to code for proteins, with recognized roles as fine regulators of gene expression. They can exert these functions through a variety of mechanisms, acting at almost all steps of gene expression, from modulation of the epigenetic state of chromatin to modulation of protein stability. In all cases, lncRNAs do not work alone, but they always interact with other RNA molecules, either coding or non-coding, or with protein factors. In this review, we summarize the latest results obtained about the involvement of lncRNAs in the initiating cells of several types of tumors, and highlight the different mechanisms through which they work, while discussing how the modulation of a lncRNA can affect several aspects of tumor onset and progression. [ABSTRACT FROM AUTHOR]

Globally, pancreatic ductal adenocarcinoma remains among the most aggressive forms of neoplastic diseases, having a dismal prognostic outcome. Recent findings elucidated that epithelial–mesenchymal transition (EMT) can play an important role in pancreatic tumorigenic processes, as it contributes to the manifestation of malignant proliferative masses, which impede adequate drug delivery. An organized literature search with PubMed, Scopus, Microsoft Academic and the Cochrane library was performed for articles published in English from 2011 to 2021 to review and summarize the latest updates and knowledge on the current understanding of EMT and its implications for tumorigenesis and chemoresistance. Furthermore, in the present paper, we investigate the recent findings on metformin as a possible neoadjuvant chemotherapy agent, which affects EMT progression and potentially provides superior oncological outcomes for PDAC patients. Our main conclusions indicate that selectively suppressing EMT in pancreatic cancer cells has a promising therapeutic utility by selectively targeting the chemotherapy-resistant sub-population of cancer stem cells, inhibiting tumor growth via EMT pathways and thereby improving remission in PDAC patients. Moreover, given that TGF-β1-driven EMT generates the migration of tumor-initiating cells by directly linking the acquisition of abnormal cellular motility with the maintenance of tumor initiating potency, the chemoprevention of TGF-β1-induced EMT may have promising clinical applications in the therapeutic management of PDAC outcomes. [ABSTRACT FROM AUTHOR]

Seed oils are the richest source of vitamin-E-active compounds, which contribute significantly to antioxidant activities. Cottonseed oil (CS-O) is attaining more consideration owing to its high fiber content and stability against auto-oxidation. CS-O has gained a good reputation in the global edible oil market due to its distinctive fatty acid profile, anti-inflammatory, and cardio-protective properties. CS-O can be extracted from cottonseed (CS) by microwave-assisted extraction (MAE), aqueous/solvent extraction (A/SE), aqueous ethanol extraction (A-EE), subcritical water extraction, supercritical carbon dioxide extraction (SC-CO2), and enzyme-assisted extraction (E-AE). In this review, the importance, byproducts, physicochemical characteristics, and nutritional profile of CS-O have been explained in detail. This paper also provides a summary of scientific studies existing on functional and phytochemical characteristics of CS-O. Its consumption and health benefits are also deliberated to discover its profitability and applications. CS-O contains 26-35% saturated, 42-52% polyunsaturated, and 18-24% monounsaturated FA. There is approximately 1000 ppm of tocopherols in unprocessed CS-O, but up to one-third is lost during processing. Moreover, besides being consumed as cooking oil, CS-O discovers applications in many fields such as biofuel, livestock, cosmetics, agriculture, and chemicals. This paper provides a comprehensive review of CS-O, its positive benefits, fatty acid profile, extraction techniques, and health applications. CS-O is a rich source of exceptional fatty acids. Various techniques to extract the CS-O are discussed. Numerous physicochemical properties of CS-O for the potential market are assessed. It has a wide range of functional properties. Nutritional quality and health benefits are also evaluated. [ABSTRACT FROM AUTHOR]

Uterine leiomyomas (ULs), frequent benign tumours of the female reproductive tract, are associated with a range of symptoms and significant morbidity. Despite extensive research, there is no consensus on essential points of UL initiation and development. The main reason for this is a pronounced inter- and intratumoral heterogeneity resulting from diverse and complicated mechanisms underlying UL pathobiology. In this review, we comprehensively analyse risk and protective factors for UL development, UL cellular composition, hormonal and paracrine signalling, epigenetic regulation and genetic abnormalities. We conclude the need to carefully update the concept of UL genesis in light of the current data. Staying within the framework of the existing hypotheses, we introduce a possible timeline for UL development and the associated key events—from potential prerequisites to the beginning of UL formation and the onset of driver and passenger changes. [ABSTRACT FROM AUTHOR]

While epidemiological data are available for the dose and dose-rate effectiveness factor (DDREF) for human populations, animal models have contributed significantly to providing quantitative data with mechanistic insights. The aim of the current review is to compile both the in vitro experiments with reference to the dose-rate effects of DNA damage and repair, and the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. In particular, the review focuses especially on the results pertaining to underlying biological mechanisms and discusses their possible involvement in the process of radiation-induced carcinogenesis. Because the concept of adverse outcome pathway (AOP) together with the key events has been considered as a clue to estimate radiation risks at low doses and low dose-rates, the review scrutinized the dose-rate dependency of the key events related to carcinogenesis, which enables us to unify the underlying critical mechanisms to establish a connection between animal experimental studies with human epidemiological studies. [ABSTRACT FROM AUTHOR]

Microglia are the primary immunocompetent cells of the central nervous system (CNS). Their ability to survey, assess and respond to perturbations in their local environment is critical in their role of maintaining CNS homeostasis in health and disease. Microglia also have the capability of functioning in a heterogeneous manner depending on the nature of their local cues, as they can become activated on a spectrum from pro-inflammatory neurotoxic responses to anti-inflammatory protective responses. This review seeks to define the developmental and environmental cues that support microglial polarization towards these phenotypes, as well as discuss sexually dimorphic factors that can influence this process. Further, we describe a variety of CNS disorders including autoimmune disease, infection, and cancer that demonstrate disparities in disease severity or diagnosis rates between males and females, and posit that microglial sexual dimorphism underlies these differences. Understanding the mechanism behind differential CNS disease outcomes between men and women is crucial in the development of more effective targeted therapies. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma, bladder cancer, and prostate cancer are the most widespread genitourinary tumors. Their treatment and diagnosis have significantly evolved over recent years, due to an increasing understanding of oncogenic factors and the molecular mechanisms involved. Using sophisticated genome sequencing technologies, the non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have all been implicated in the occurrence and progression of genitourinary cancers. Interestingly, DNA, protein, and RNA interactions with lncRNAs and other biological macromolecules drive some of these cancer phenotypes. Studies on the molecular mechanisms of lncRNAs have identified new functional markers that could be potentially useful as biomarkers for effective diagnosis and/or as targets for therapeutic intervention. This review focuses on the mechanisms underlying abnormal lncRNA expression in genitourinary tumors and discusses their role in diagnostics, prognosis, and treatment. [ABSTRACT FROM AUTHOR]

Ongoing research has revealed that the existence of cancer stem cells (CSCs) is one of the biggest obstacles in the current cancer therapy. CSCs make an influential function in tumor progression, recurrence and chemoresistance due to their typical stemness characteristics. CSCs are preferentially distributed in niches, and those niche sites exhibit characteristics typical of the tumor microenvironment (TME). The complex interactions between CSCs and TME illustrate these synergistic effects. The phenotypic heterogeneity within CSCs and the spatial interactions with the surrounding tumor microenvironment led to increased therapeutic challenges. CSCs interact with immune cells to protect themselves against immune clearance by exploiting the immunosuppressive function of multiple immune checkpoint molecules. CSCs also can protect themselves against immune surveillance by excreting extracellular vesicles (EVs), growth factors, metabolites and cytokines into the TME, thereby modulating the composition of the TME. Therefore, these interactions are also being considered for the therapeutic development of anti-tumor agents. We discuss here the immune molecular mechanisms of CSCs and comprehensively review the interplay between CSCs and the immune system. Thus, studies on this topic seem to provide novel ideas for reinvigorating therapeutic approaches to cancer. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly aggressive malignancy with a climbing incidence. The majority of cases are detected late, with incurable locally advanced or metastatic disease. Even in individuals who undergo resection, recurrence is unfortunately very common. There is no universally accepted screening modality for the general population and diagnosis, evaluation of treatment response, and detection of recurrence relies primarily on the use of imaging. Identification of minimally invasive techniques to help diagnose, prognosticate, predict response or resistance to therapy, and detect recurrence are desperately needed. Liquid biopsies represent an emerging group of technologies which allow for non-invasive serial sampling of tumor material. Although not yet approved for routine use in pancreatic cancer, the increasing sensitivity and specificity of contemporary liquid biopsy platforms will likely change clinical practice in the near future. In this review, we discuss the recent technological advances in liquid biopsy, focusing on circulating tumor DNA, exosomes, microRNAs, and circulating tumor cells. [ABSTRACT FROM AUTHOR]

The concept of the Myc (c-myc, n-myc, l-myc) oncogene as a canonical, DNA-bound transcription factor has consistently changed over the past few years. Indeed, Myc controls gene expression programs at multiple levels: directly binding chromatin and recruiting transcriptional coregulators; modulating the activity of RNA polymerases (RNAPs); and drawing chromatin topology. Therefore, it is evident that Myc deregulation in cancer is a dramatic event. Glioblastoma multiforme (GBM) is the most lethal, still incurable, brain cancer in adults, and it is characterized in most cases by Myc deregulation. Metabolic rewiring typically occurs in cancer cells, and GBM undergoes profound metabolic changes to supply increased energy demand. In nontransformed cells, Myc tightly controls metabolic pathways to maintain cellular homeostasis. Consistently, in Myc-overexpressing cancer cells, including GBM cells, these highly controlled metabolic routes are affected by enhanced Myc activity and show substantial alterations. On the other hand, deregulated cancer metabolism impacts Myc expression and function, placing Myc at the intersection between metabolic pathway activation and gene expression. In this review paper, we summarize the available information on GBM metabolism with a specific focus on the control of the Myc oncogene that, in turn, rules the activation of metabolic signals, ensuring GBM growth. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and the fourth leading cause of cancer-related death globally. Tumor cells recruit and remodel various types of stromal and inflammatory cells to form a tumor microenvironment (TME), which encompasses cellular and molecular entities, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), immune cells, myeloid-derived suppressor cells (MDSCs), immune checkpoint molecules and cytokines that promote cancer cell growth, as well as their drug resistance. HCC usually arises in the context of cirrhosis, which is always associated with an enrichment of activated fibroblasts that are owed to chronic inflammation. CAFs are a major component of the TME, providing physical support in it and secreting various proteins, such as extracellular matrices (ECMs), hepatocyte growth factor (HGF), insulin-like growth factor 1/2 (ILGF1/2) and cytokines that can modulate tumor growth and survival. As such, CAF-derived signaling may increase the pool of resistant cells, thus reducing the duration of clinical responses and increasing the degree of heterogeneity within tumors. Although CAFs are often implicated to be associated with tumor growth, metastasis and drug resistance, several studies have reported that CAFs have significant phenotypic and functional heterogeneity, and some CAFs display antitumor and drug-sensitizing properties. Multiple studies have highlighted the relevance of crosstalk between HCC cells, CAFs and other stromal cells in influence of HCC progression. Although basic and clinical studies partially revealed the emerging roles of CAFs in immunotherapy resistance and immune evasion, a better understanding of the unique functions of CAFs in HCC progression will contribute to development of more effective molecular-targeted drugs. In this review article, molecular mechanisms involved in crosstalk between CAFs, HCC cells and other stromal cells, as well as the effects of CAFs on HCC-cell growth, metastasis, drug resistance and clinical outcomes, are comprehensively discussed. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is today the sixth leading cause of cancer-related death worldwide, despite the decreased incidence of chronic hepatitis infections. This is due to the increased diffusion of metabolic diseases such as the metabolic syndrome, diabetes, obesity, and nonalcoholic steatohepatitis (NASH). The current protein kinase inhibitor therapies in HCC are very aggressive and not curative. From this perspective, a shift in strategy toward metabolic therapies may represent a promising option. Here, we review current knowledge on metabolic dysregulation in HCC and therapeutic approaches targeting metabolic pathways. We also propose a multi-target metabolic approach as a possible new option in HCC pharmacology. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Along with apoptosis and inflammation, autophagy is one of three important mechanisms in CRC. The presence of autophagy/mitophagy in most normal mature intestinal epithelial cells has been confirmed, where it has mainly protective functions against reactive oxygen species (ROS)-induced DNA and protein damage. Autophagy regulates cell proliferation, metabolism, differentiation, secretion of mucins and/or anti-microbial peptides. Abnormal autophagy in intestinal epithelial cells leads to dysbiosis, a decline in local immunity and a decrease in cell secretory function. The insulin-like growth factor (IGF) signaling pathway plays an important role in colorectal carcinogenesis. This is evidenced by the biological activities of IGFs (IGF-1 and IGF-2), IGF-1 receptor type 1 (IGF-1R) and IGF-binding proteins (IGF BPs), which have been reported to regulate cell survival, proliferation, differentiation and apoptosis. Defects in autophagy are found in patients with metabolic syndrome (MetS), inflammatory bowel diseases (IBD) and CRC. In neoplastic cells, the IGF system modulates the autophagy process bidirectionally. In the current era of improving CRC therapies, it seems important to investigate the exact mechanisms not only of apoptosis, but also of autophagy in different populations of tumor microenvironment (TME) cells. The role of the IGF system in autophagy in normal as well as transformed colorectal cells still seems poorly understood. Hence, the aim of the review was to summarize the latest knowledge on the role of the IGF system in the molecular mechanisms of autophagy in the normal colon mucosa and in CRC, taking into account the cellular heterogeneity of the colonic and rectal epithelium. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause of cancer death among women worldwide. Globally, BC is the second most frequent cancer and first most frequent gynecological one, affecting women with a relatively low case-mortality rate. Surgery, radiotherapy, and chemotherapy are the main treatments for BC, even though the latter are often not aways successful because of the common side effects and the damage caused to healthy tissues and organs. Aggressive and metastatic BCs are difficult to treat, thus new studies are needed in order to find new therapies and strategies for managing these diseases. In this review, we intend to give an overview of studies in this field, presenting the data from the literature concerning the classification of BCs and the drugs used in therapy for the treatment of BCs, along with drugs in clinical studies. [ABSTRACT FROM AUTHOR]

Ferroptosis was first reported as a separate modality of regulated cell death in 2008 and distinguished under its current name in 2012 after it was first induced with erastin. In the following decade, multiple other chemical agents were researched for their pro- or anti-ferroptotic properties. Complex organic structures with numerous aromatic moieties make up the majority of this list. This review fills a more overlooked niche by gathering, outlining and setting out conclusions regarding less prominent cases of ferroptosis induced by bioinorganic compounds and reported on within the last few years. The article contains a short summary of the application of bioinorganic chemicals based on gallium, several chalcogens, transition metals and elements known as human toxicants used for the purpose of evoking ferroptotic cell death in vitro or in vivo. These are used in the form of free ions, salts, chelates, gaseous and solid oxides or nanoparticles. Knowledge of how exactly these modulators promote or inhibit ferroptosis could be beneficial in the context of future therapies aimed against cancer or neurodegenerative diseases, respectively. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) have been identified and characterized in both hematopoietic and solid tumors. Their existence was first predicted by Virchow and Cohnheim in the 1870s. Later, many studies showed that CSCs can be identified and isolated by their expression of specific cell markers. The significance of CSCs with respect to tumor biology and anti-cancer treatment lies in their ability to maintain quiescence with very slow proliferation, indefinite self-renewal, differentiation, and trans-differentiation such as epithelial–mesenchymal transition (EMT) and its reverse process mesenchymal–epithelial transition (MET). The ability for detachment, migration, extra- and intravasation, invasion and thereby of completing all necessary steps of the metastatic cascade highlights their significance for metastasis. CSCs comprise the cancer cell populations responsible for tumor growth, resistance to therapies and cancer metastasis. In this review, the history of the CSC theory, their identification and characterization and their biology are described. The contribution of the CSC ability to undergo EMT for cancer metastasis is discussed. Recently, novel strategies for drug development have focused on the elimination of the CSCs specifically. The unique functional and molecular properties of CSCs are discussed as possible therapeutic vulnerabilities for the development of novel anti-metastasis treatments. Prospectively, this may provide precise personalized anti-cancer treatments with improved therapeutic efficiency with fewer side effects and leading to better prognosis. [ABSTRACT FROM AUTHOR]

Cancer cells undergo metabolic reprogramming and switch to a 'glycolysis-dominant' metabolic profile to promote their survival and meet their requirements for energy and macromolecules. This phenomenon, also known as the 'Warburg effect,' provides a survival advantage to the cancer cells and make the tumor environment more pro-cancerous. Additionally, the increased glycolytic dependence also promotes chemo/radio resistance. A similar switch to a glycolytic metabolic profile is also shown by the immune cells in the tumor microenvironment, inducing a competition between the cancer cells and the tumor-infiltrating cells over nutrients. Several recent studies have shown that targeting the enhanced glycolysis in cancer cells is a promising strategy to make them more susceptible to treatment with other conventional treatment modalities, including chemotherapy, radiotherapy, hormonal therapy, immunotherapy, and photodynamic therapy. Although several targeting strategies have been developed and several of them are in different stages of pre-clinical and clinical evaluation, there is still a lack of effective strategies to specifically target cancer cell glycolysis to improve treatment efficacy. Herein, we have reviewed our current understanding of the role of metabolic reprogramming in cancer cells and how targeting this phenomenon could be a potential strategy to improve the efficacy of conventional cancer therapy. [ABSTRACT FROM AUTHOR]

Liver cancers are rising worldwide. Between molecular and epidemiological studies, a research gap has emerged which might be amenable to the technique of metabolomics. This review investigates the current understanding of liver cancer's trends, etiology and its correlates with existing literature for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA) and hepatoblastoma (HB). Among additional factors, the literature reports dysfunction in the tricarboxylic acid metabolism, primarily for HB and HCC, and point mutations and signaling for CCA. All cases require further investigation of upstream and downstream events. All liver cancers reported dysfunction in the WNT/β-catenin and P13K/AKT/mTOR pathways as well as changes in FGFR. Metabolites of IHD1, IDH2, miRNA, purine, Q10, lipids, phosphatidylcholine, phosphatidylethanolamine, acylcarnitine, 2-HG and propionyl-CoA emerged as crucial and there was an attempt to elucidate the WNT/β-catenin and P13K/AKT/mTOR pathways metabolomically. [ABSTRACT FROM AUTHOR]

In this review we focus on the role of glutamine in control of cancer stem cell (CSC) fate. We first provide an overview of glutamine metabolism, and then summarize relevant studies investigating how glutamine metabolism modulates the CSC compartment, concentrating on solid tumors. We schematically describe how glutamine in CSC contributes to several metabolic pathways, such as redox metabolic pathways, ATP production, non-essential aminoacids and nucleotides biosynthesis, and ammonia production. Furthermore, we show that glutamine metabolism is a key regulator of epigenetic modifications in CSC. Finally, we briefly discuss how cancer-associated fibroblasts, adipocytes, and senescent cells in the tumor microenvironment may indirectly influence CSC fate by modulating glutamine availability. We aim to highlight the complexity of glutamine's role in CSC, which supports our knowledge about metabolic heterogeneity within the CSC population. [ABSTRACT FROM AUTHOR]

Cancer stem cells are found in many cancer types. They comprise a distinct subpopulation of cells within the tumor that exhibit properties of stem cells. They express a number of cell surface markers, such as CD133, CD44, ALDH, and EpCAM, as well as embryonic transcription factors Oct4, Nanog, and SOX2. CSCs are more resistant to conventional chemotherapy and can potentially drive tumor relapse. Therefore, it is essential to understand the molecular mechanisms that drive chemoresistance and to target them with specific therapy effectively. Highly conserved developmental signaling pathways such as Wnt, Hedgehog, and Notch are commonly reported to play a role in CSCs chemoresistance development. Studies show that particular pathway inhibitors combined with conventional therapy may re-establish sensitivity to the conventional therapy. Another significant contributor of chemoresistance is a specific tumor microenvironment. Surrounding stroma in the form of cancer-associated fibroblasts, macrophages, endothelial cells, and extracellular matrix components produce cytokines and other factors, thus creating a favorable environment and decreasing the cytotoxic effects of chemotherapy. Anti-stromal agents may potentially help to overcome these effects. Epigenetic changes and autophagy were also among the commonly reported mechanisms of chemoresistance. This review provides an overview of signaling pathway components involved in the development of chemoresistance of CSCs and gathers evidence from experimental studies in which CSCs can be re-sensitized to conventional chemotherapy agents across different cancer types. [ABSTRACT FROM AUTHOR]

Cancer stem cells are known to play a key role in tumour development, proliferation, and metastases. Their unique properties confer resistance to therapy, often leading to treatment failure. It is believed that research into the identification, targeting, and eradication of these cells can revolutionise oncological treatment. Based on the principle that what cannot be seen, cannot be targeted, a primary step in cancer management is the identification of these cells. The current review aims to encompass the state-of-the-art functional imaging techniques that enable the identification of cancer stem cells via various pathways and mechanisms. The paper presents in vivo molecular techniques that are currently available or await clinical implementation. Challenges and future prospects are highlighted to open new research avenues in cancer stem cell imaging. [ABSTRACT FROM AUTHOR]

The carcinogenesis of glial tumors appears complex because of the many genetic and epigenetic phenomena involved. Among these, cellular prion protein (PrPC) is considered a key factor in cell-death resistance and important aspect implicated in tumorigenesis. Autophagy also plays an important role in cell death in various pathological conditions. These two cellular phenomena are related and share the same activation by specific alterations in the cellular microenvironment. Furthermore, there is an interdependence between autophagy and prion activity in glioma tumorigenesis. Glioma is one of the most aggressive known cancers, and the fact that such poorly studied processes as autophagy and PrPC activity are so strongly involved in its carcinogenesis suggests that by better understanding their interaction, more can be understood about its origin and treatment. Few studies in the literature relate these two cellular phenomena, much less try to explain their combined activity and role in glioma carcinogenesis. In this study, we explored the recent findings on the molecular mechanism and regulation pathways of autophagy, examining the role of PrPC in autophagy processes and how they may play a central role in glioma tumorigenesis. Among the many molecular interactions that PrP physiologically performs, it appears that processes shared with autophagy activity are those most implicated in glial tumor carcinogeneses such as activity on MAP kinases, PI3K, and mTOR. This work can be supportive and valuable as a basis for further future studies on this topic. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma are devastating primary liver cancers with increasing prevalence in many parts of the world. Despite intense investigation, many aspects of their biology are still largely obscure. For example, numerous studies have tackled the question of the cell-of-origin of primary liver cancers using different experimental approaches; they have not, however, provided a clear and undisputed answer. Here, we will review the evidence from animal models supporting the role of all major types of liver epithelial cells: hepatocytes, cholangiocytes, and their common progenitor as liver cancer cell-of-origin. Moreover, we will also propose mechanisms that promote liver cancer cell plasticity (dedifferentiation, transdifferentiation, and epithelial-to-mesenchymal transition) which may contribute to misinterpretation of the results and which make the issue of liver cancer cell-of-origin particularly complex. [ABSTRACT FROM AUTHOR]

In recent years, the study of anticancer bioactive compounds from marine sources has received wide interest. Contextually, world regulatory authorities have approved several marine molecules, and new synthetic derivatives have also been synthesized and structurally improved for the treatment of numerous forms of cancer. However, the administration of drugs in cancer patients requires careful evaluation since their interaction with individual biological macromolecules, such as proteins or nucleic acids, determines variable downstream effects. This is reflected in a constant search for personalized therapies that lay the foundations of modern medicine. The new knowledge acquired on cancer mechanisms has certainly allowed advancements in tumor prevention, but unfortunately, due to the huge complexity and heterogeneity of cancer, we are still looking for a definitive therapy and clinical approaches. In this review, we discuss the significance of recently approved molecules originating from the marine environment, starting from their organism of origin to their structure and mechanism of action. Subsequently, these bio-compounds are used as models to illustrate possible bioinformatics approaches for the search of new targets that are useful for improving the knowledge on anticancer therapies. [ABSTRACT FROM AUTHOR]

Cancer divergence has many facets other than being considered a genetic term. It is a tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates the opportunity to explore the possible mechanism in the surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their tumor microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, and fibroblast cells. Cancer stem cells (CSCs) or cancer stem-like cells are a small sub-set of the population within cancer cells believed to be a responsible player in the self-renewal, metastasis, and therapy response of cancer cells. The correlation between TME and CSCs remains an enigma in understanding the events of metastasis and therapy resistance in cancer biology. Recent evidence suggests that TME dictates the CSCs maintenance to arbitrate cancer progression and metastasis. The immune, inflammatory, endothelial, adipocyte, and fibroblast cells in the TME release growth factors, cytokines, chemokines, microRNAs, and exosomes that provide cues for the gain and maintenance of CSC features. These intricate cross-talks are fueled to evolve into aggressive, invasive, migratory phenotypes for cancer development. In this review, we have abridged the recent developments in the role of the TME factors in CSC maintenance and how these events influence the transition of tumor progression to further translate into metastasis and therapy resistance in cancer. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is a malignancy that is becoming increasingly common in adolescents. OS stem cells (OSCs) form a dynamic subset of OS cells that are responsible for malignant progression and chemoradiotherapy resistance. The unique properties of OSCs, including self-renewal, multilineage differentiation and metastatic potential, 149 depend closely on their tumor microenvironment. In recent years, the likelihood of its dynamic plasticity has been extensively studied. Importantly, the tumor microenvironment appears to act as the main regulatory component of OS cell plasticity. For these reasons aforementioned, novel strategies for OS treatment focusing on modulating OS cell plasticity and the possibility of modulating the composition of the tumor microenvironment are currently being explored. In this paper, we review recent studies describing the phenomenon of OSCs and factors known to influence phenotypic plasticity. The microenvironment, which can regulate OSC plasticity, has great potential for clinical exploitation and provides different perspectives for drug and treatment design for OS. [ABSTRACT FROM AUTHOR]

Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate. [ABSTRACT FROM AUTHOR]

Breast cancer, as a highly heterogeneous malignant tumor, is one of the primary causes of death among females worldwide. The etiology of breast cancer involves aberrant epigenetic mechanisms and abnormal expression of certain non-coding RNA (ncRNAs). DNA methylation, N6-methyladenosine(m6A), and histone methylation are widely explored epigenetic regulation types in breast cancer. ncRNAs are a group of unique RNA transcripts, mainly including microRNA (miRNAs), long non-coding RNA (lncRNAs), circular RNA (circRNAs), small interfering RNA (siRNAs), piwi-interacting RNA (piRNAs), etc. Different types of methylation and ncRNAs mutually regulate and interact to form intricate networks to mediate precisely breast cancer genesis. In this review, we elaborate on the crosstalk between major methylation modifications and ncRNAs and discuss the role of their interaction in promoting breast cancer oncogenesis. This review can provide novel insights into establishing a new diagnostic marker system on methylation patterns of ncRNAs and therapeutic perspectives of combining ncRNA oligonucleotides and phytochemical drugs for breast cancer therapy. [ABSTRACT FROM AUTHOR]

Flavones are natural phytochemicals broadly distributed in our diet. Their anti-inflammatory properties provide unique opportunities to control the innate immune system and inflammation. Here, we review the role of flavones in chronic inflammation with an emphasis on their impact on the molecular mechanisms underlying inflammatory diseases including obesity and cancer. Flavones can influence the innate immune cell repertoire restoring the immune landscape. Flavones impinge on NF-κB, STAT, COX-2, or NLRP3 inflammasome pathways reestablishing immune homeostasis. Devoid of adverse side effects, flavones could present alternative opportunities for the treatment and prevention of chronic inflammation that contributes to obesity and cancer. [ABSTRACT FROM AUTHOR]

Evidence is accumulating that the tumour microenvironment (TME) has a key role in the progression of gliomas. Non-neoplastic cells in addition to the tumour cells are therefore finding increasing attention. Microglia and other glioma-associated macrophages are at the centre of this interest especially in the context of therapeutic considerations. New ideas have emerged regarding the role of microglia and, more recently, blood-derived brain macrophages in glioblastoma (GBM) progression. We are now beginning to understand the mechanisms that allow malignant glioma cells to weaken microglia and brain macrophage defence mechanisms. Surface molecules and cytokines have a prominent role in microglia/macrophage-glioma cell interactions, and we discuss them in detail. The involvement of exosomes and microRNAs forms another focus of this review. In addition, certain microglia and glioma cell pathways deserve special attention. These "synergistic" (we suggest calling them "Janus") pathways are active in both glioma cells and microglia/macrophages where they act in concert supporting malignant glioma progression. Examples include CCN4 (WISP1)/Integrin α6β1/Akt and CHI3L1/PI3K/Akt/mTOR. They represent attractive therapeutic targets. [ABSTRACT FROM AUTHOR]

Tumours are complex systems with dynamic interactions between tumour cells, non-tumour cells, and extracellular components that comprise the tumour microenvironment (TME). The majority of TME's cells are cancer-associated fibroblasts (CAFs), which are crucial in extracellular matrix (ECM) construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour cell motility. CAF subtypes have been identified based on the expression of protein markers. CAFs may act as promoters or suppressors in tumour cells depending on a variety of factors, including cancer stage. Indeed, CAFs have been shown to promote tumour growth, survival and spread, and secretome changes, but they can also slow tumourigenesis at an early stage through mechanisms that are still poorly understood. Stromal–cancer interactions are governed by a variety of soluble factors that determine the outcome of the tumourigenic process. Cancer cells release factors that enhance the ability of fibroblasts to secrete multiple tumour-promoting chemokines, acting on malignant cells to promote proliferation, migration, and invasion. This crosstalk between CAFs and tumour cells has given new prominence to the stromal cells, from being considered as mere physical support to becoming key players in the tumour process. Here, we focus on the concept of cancer as a non-healing wound and the relevance of chronic inflammation to tumour initiation. In addition, we review CAFs heterogeneous origins and markers together with the potential therapeutic implications of CAFs "re-education" and/or targeting tumour progression inhibition. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are currently incurable. Numerous experimental data accumulated over the past fifty years have brought us closer to understanding the molecular and cell mechanisms responsible for their development. However, these data are not enough for a complete understanding of the genesis of these diseases, nor to suggest treatment methods. It turns out that many cellular pathologies developing during neurodegeneration coincide from disease to disease. These observations give hope to finding a common intracellular target(s) and to offering a universal method of treatment. In this review, we attempt to analyze data on similar cellular disorders among neurodegenerative diseases in general, and polyglutamine neurodegenerative diseases in particular, focusing on the interaction of various proteins involved in the development of neurodegenerative diseases with various cellular organelles. The main purposes of this review are: (1) to outline the spectrum of common intracellular pathologies and to answer the question of whether it is possible to find potential universal target(s) for therapeutic intervention; (2) to identify specific intracellular pathologies and to speculate about a possible general approach for their treatment. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolization (TACE) is generally used to treat patients with hepatocellular carcinoma (HCC), a common and deadly cancer; however, its efficacy varies according to factors such as tumor volume, stage, serum alpha-fetoprotein level, and chosen feeding artery. In addition, gene-related factors have been recently suggested to be involved in the regulation and prediction of TACE outcomes. Accordingly, genes could serve as effective biomarkers to select patients who can benefit from TACE. These gene-related factors can activate signaling pathways affecting cancer cell survival while regulating the epithelial–mesenchymal transition, angiogenesis, and the tumor microenvironment, all directly associated with tumor progression, thereby affecting TACE efficacy. Moreover, this disordered gene expression is associated with poor prognosis in patients with HCC, including TACE resistance, postoperative recurrence, and metastasis. To identify the exact relationship between various genes and TACE efficacy, this review summarizes the involvement of protein-coding and non-coding genes and single nucleotide polymorphisms in TACE efficacy for predicting the efficacy of TACE; the present findings may help improve the efficacy of TACE in clinical settings. [ABSTRACT FROM AUTHOR]

The most common and aggressive primitive intracranial tumor of the central nervous system is the glioma. The blood–brain barrier (BBB) has proven to be a significant obstacle to the effective treatment of glioma. To effectively treat glioma, different ways have been used to cross the BBB to deliver drugs to the brain. Drug delivery through nanocarriers proves to be an effective and non-invasive technique for the treatment of glioma and has great potential in the treatment of glioma. In this review, we will provide an overview of nanocarrier-mediated drug delivery and related glioma therapy. Nanocarrier-mediated drug delivery techniques to cross the BBB (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, and biomimetic nanoparticles) are explored. Finally, the use of nanotherapeutic approaches in the treatment of glioblastoma including chemotherapy, radiotherapy, photothermal therapy, gene therapy, glioma genome editing, immunotherapy, chimeric antigen receptor (CAR) T-cells, immune checkpoint modulators, immune photothermal therapy, vaccine-based immunotherapy, and combination therapy is summarized. Furthermore, this article offers various views on the clinical applicability of nanomedicine. [ABSTRACT FROM AUTHOR]

Despite the significant progress in decreasing the occurrence and mortality of hepatocellular carcinoma (HCC), it remains a public health issue worldwide on the basis of its late presentation and tumor recurrence. To date, apart from surgical interventions, such as surgical resection, liver transplantation and locoregional ablation, current standard antitumor protocols include conventional cytotoxic chemotherapy. However, due to the high chemoresistance nature, most current therapeutic agents show dismal outcomes for this refractory malignancy, leading to disease relapse. Nevertheless, the molecular mechanisms involved in chemotherapy resistance remain systematically ambiguous. Herein, HCC is hierarchically characterized by the formation of primitive cancer stem cells (CSCs), progression of epithelial-mesenchymal transition (EMT), unbalanced autophagy, delivery of extracellular vesicles (EVs), escape of immune surveillance, disruption of ferroptosis, alteration of the tumor microenvironment and multidrug resistance-related signaling pathways that mediate the multiplicity and complexity of chemoresistance. Of note, anecdotal evidence has corroborated that noncoding RNAs (ncRNAs) extensively participate in the critical physiological processes mentioned above. Therefore, understanding the detailed regulatory bases that underlie ncRNA-mediated chemoresistance is expected to yield novel insights into HCC treatment. In the present review, a comprehensive summary of the latest progress in the investigation of chemotherapy resistance concerning ncRNAs will be elucidated to promote tailored individual treatment for HCC patients. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a serious public health issue, and it has the leading incidence and mortality among malignant tumors worldwide. CRC patients with metastasis in the liver, lung or other distant sites always have poor prognosis. Thus, there is an urgent need to discover the underlying mechanisms of metastatic colorectal cancer (mCRC) and to develop optimal therapy for mCRC. Transforming growth factor-β (TGF-β) signaling plays a significant role in various physiologic and pathologic processes, and aberrant TGF-β signal transduction contributes to mCRC progression. In this review, we summarize the alterations of the TGF-β signaling pathway in mCRC patients, the functional mechanisms of TGF-β signaling, its promotion of epithelial–mesenchymal transition, its facilitation of angiogenesis, its suppression of anti-tumor activity of immune cells in the microenvironment and its contribution to stemness of CRC cells. We also discuss the possible applications of TGF-β signaling in mCRC diagnosis, prognosis and targeted therapies in clinical trials. Hopefully, these research advances in TGF-β signaling in mCRC will improve the development of new strategies that can be combined with molecular targeted therapy, immunotherapy and traditional therapies to achieve better efficacy and benefit mCRC patients in the near future. [ABSTRACT FROM AUTHOR]

Glioma is the most common type of primary CNS tumor, composed of cells that resemble normal glial cells. Recent genetic studies have provided insight into the inter-tumoral heterogeneity of gliomas, resulting in the updated 2021 WHO classification of gliomas. Thorough understanding of inter-tumoral heterogeneity has already improved the prognosis and treatment outcomes of some types of gliomas. Currently, the challenge for researchers is to study the intratumoral cell heterogeneity of newly defined glioma subtypes. Cancer stem cells (CSCs) present in gliomas and many other tumors are an example of intratumoral heterogeneity of great importance. In this review, we discuss the modern concept of glioma stem cells and recent single-cell sequencing-driven progress in the research of intratumoral glioma cell heterogeneity. The particular emphasis was placed on the recently revealed variations of the cell composition of the subtypes of the adult-type diffuse gliomas, including astrocytoma, oligodendroglioma and glioblastoma. The novel data explain the inconsistencies in earlier glioma stem cell research and also provide insight into the development of more effective targeted therapy and the cell-based immunotherapy of gliomas. Separate sections are devoted to the description of single-cell sequencing approach and its role in the development of cell-based immunotherapies for glioma. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) diseases, such as multiple sclerosis, Alzheimer's disease (AD), and Parkinson's disease (PD), affect millions of people around the world. Great efforts were put in disease related research, but few breakthroughs have been made in the diagnostic and therapeutic approaches. Exosomes are cell-derived extracellular vesicles containing diverse biologically active molecules secreted by their cell of origin. These contents, including nucleic acids, proteins, lipids, amino acids, and metabolites, can be transferred between different cells, tissues, or organs, regulating various intercellular cross-organ communications and normal and pathogenic processes. Considering that cellular environment and cell state strongly impact the content and uptake efficiency of exosomes, their detection in biological fluids and content composition analysis potentially offer a multicomponent diagnostic readout of several human diseases. Recently, studies have found that aberrant secretion and content of exosomes are closely related to the pathogenesis of CNS diseases. Besides, loading natural cargoes, exosomes can deliver drugs cross the blood brain barrier, making them emerging candidates of biomarkers and therapeutics for CNS diseases. In this review, we summarize and discuss the advanced research progress of exosomes in the pathological processes of several CNS diseases in regarding with neuroinflammation, CNS repair, and pathological protein aggregation. Moreover, we propose the therapeutic strategies of applying exosomes to the diagnosis, early detection, and treatment of CNS diseases. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of death in colorectal cancer (CRC) patients, and the liver is the most common site of metastasis. Tumor cell metastasis can be thought of as an invasion-metastasis cascade and metastatic organotropism is thought to be a process that relies on the intrinsic properties of tumor cells and their interactions with molecules and cells in the microenvironment. Many studies have provided new insights into the molecular mechanism and contributing factors involved in CRC liver metastasis for a better understanding of the organ-specific metastasis process. The purpose of this review is to summarize the theories that explain CRC liver metastasis at multiple molecular dimensions (including genetic and non-genetic factors), as well as the main factors that cause CRC liver metastasis. Many findings suggest that metastasis may occur earlier than expected and with specific organ-anchoring property. The emergence of potential metastatic clones, the timing of dissemination, and the distinct routes of metastasis have been explained by genomic studies. The main force of CRC liver metastasis is also thought to be epigenetic alterations and dynamic phenotypic traits. Furthermore, we review key extrinsic factors that influence CRC cell metastasis and liver tropisms, such as pre-niches, tumor stromal cells, adhesion molecules, and immune/inflammatory responses in the tumor microenvironment. In addition, biomarkers associated with early diagnosis, prognosis, and recurrence of liver metastasis from CRC are summarized to enlighten potential clinical practice, including some markers that can be used as therapeutic targets to provide new perspectives for the treatment strategies of CRC liver metastasis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) have not yielded significant efficacy in pancreatic ductal adenocarcinoma (PDA), despite the role of the innate and adaptive immune systems on progression and survival. However, recently identified pathways have identified new targets and generated promising clinical investigations into promoting an effective immune-mediated antitumor response in PDA. We review biological mechanisms associated with immunotherapy resistance and outline strategies for therapeutic combinations with established and novel therapies in PDA. Pancreatic cancers rarely benefit from treatment with ICI due to an immunosuppressive tumor microenvironment (TME). New understandings of factors associated with the suppressive TME include low- and poor-quality neoantigens, constrained effector T cells infiltration, and the presence of a dense, suppressive myeloid cell population. These findings have been translated into new clinical investigations evaluating novel therapies in combination with ICI and/or standard systemic chemotherapy and radiotherapy. The epithelial, immune, and stromal compartments are intricately related in PDA, and the framework for successful targeting of this disease requires a comprehensive and personalized approach. [ABSTRACT FROM AUTHOR]

Ionizing radiation (IR) has been shown to play a crucial role in the treatment of glioblastoma (GBM; grade IV) and non-small-cell lung cancer (NSCLC). Nevertheless, recent studies have indicated that radiotherapy can offer only palliation owing to the radioresistance of GBM and NSCLC. Therefore, delineating the major radioresistance mechanisms may provide novel therapeutic approaches to sensitize these diseases to IR and improve patient outcomes. This review provides insights into the molecular and cellular mechanisms underlying GBM and NSCLC radioresistance, where it sheds light on the role played by cancer stem cells (CSCs), as well as discusses comprehensively how the cellular dormancy/non-proliferating state and polyploidy impact on their survival and relapse post-IR exposure. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for about 14% of all lung cancers. Platinum-based chemotherapy has been the only available treatment for a long time, until the introduction of immune checkpoint inhibitors (ICIs) recently changed first-line standard of care and shed light on the pivotal role of the immune system. Despite improved survival in a subset of patients, a lot of them still do not benefit from first-line chemo-immunotherapy, and several studies are investigating whether different combination strategies (with both systemic and local treatments, such as radiotherapy) may improve patient outcomes. Moreover, research of biomarkers that may be used to predict patients' outcomes is ongoing. In addition to ICIs, immunotherapy offers other different strategies, including naked monoclonal antibodies targeting tumor associated antigens, conjugated antibody, bispecific antibodies and cellular therapies. In this review, we summarize the main evidence available about the use of immunotherapy in SCLC, the rationale behind combination strategies and the studies that are currently ongoing in this setting, in order to give the reader a clear and complete view of this rapidly expanding topic. [ABSTRACT FROM AUTHOR]

Biological therapy, with its multifaceted applications, has revolutionized the treatment of tumors, mainly due to its ability to exclusively target cancer cells and reduce the adverse effects on normal tissues. This review focuses on the therapies targeting the CXCR4 and CD47 receptors. We surveyed the results of early clinical trials testing compounds classified as nonpeptides, small peptides, CXCR4 antagonists or specific antibodies whose activity reduces or completely blocks the intracellular signaling pathways and cell proliferation. We then examined antibodies and fusion proteins against CD47, the receptor that acts as a "do not eat me" signal to phagocytes escaping immune surveillance. Despite these molecules being tested in early clinical trials, some drawbacks are emerging that impair their use in practice. Finally, we examined the ImmunoGenic Surrender mechanism that involves crosstalk and co-internalization of CXCR4 and CD47 upon engagement of CXCR4 by ligands or other molecules. The favorable effect of such compounds is dual as CD47 surface reduction impact on the immune response adds to the block of CXCR4 proliferative potential. These results suggest that a combination of different therapeutic approaches has more beneficial effects on patients' survival and may pave the way for new accomplishments in personalized anticancer therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) remains the most predominant type of liver cancer with an extremely poor prognosis due to its late diagnosis and high recurrence rate. One of the culprits for HCC recurrence and metastasis is the existence of cancer stem cells (CSCs), which are a small subset of cancer cells possessing robust stem cell properties within tumors. CSCs play crucial roles in tumor heterogeneity constitution, tumorigenesis, tumor relapse, metastasis, and resistance to anti-cancer therapies. Elucidation of how these CSCs maintain their stemness features is essential for the development of CSCs-based therapy. In this review, we summarize the present knowledge of intrinsic molecules and signaling pathways involved in hepatic CSCs, especially the CSC surface markers and associated signaling in regulating the stemness characteristics and the heterogeneous subpopulations within the CSC pool. In addition, we recapitulate the effects of crucial extrinsic cellular components in the tumor microenvironment, including stromal cells and immune cells, on the modulation of hepatic CSCs. Finally, we synopsize the currently valuable CSCs-targeted therapy strategies based on intervention in these intrinsic and extrinsic molecular mechanisms, in the hope of shedding light on better clinical management of HCC patients. [ABSTRACT FROM AUTHOR]

Metastatic breast cancer (MBC) is typically an incurable disease with high mortality rates; thus, early identification of metastatic features and disease recurrence through precise biomarkers is crucial. Circulating tumor cells (CTCs) consisting of heterogeneous subpopulations with different morphology and genetic, epigenetic, and gene expression profiles represent promising candidate biomarkers for metastatic potential. The experimentally verified role of epithelial-to-mesenchymal transition in cancer dissemination has not been clearly described in BC patients, but the stemness features of CTCs strongly contributes to metastatic potency. Single CTCs have been shown to be protected in the bloodstream against recognition by the immune system through impaired interactions with T lymphocytes and NK cells, while associations of heterotypic CTC clusters with platelets, leucocytes, neutrophils, tumor-associated macrophages, and fibroblasts improve their tumorigenic behavior. In addition to single CTC and CTC cluster characteristics, we reviewed CTC evaluation methods and clinical studies in early and metastatic BCs. The variable CTC tests were developed based on specific principles and strategies. However, CTC count and the presence of CTC clusters were shown to be most clinically relevant in existing clinical trials. Despite the known progress in CTC research and sampling of BC patients, implementation of CTCs and CTC clusters in routine diagnostic and treatment strategies still requires improvement in detection sensitivity and precise molecular characterizations, focused predominantly on the role of CTC clusters for their higher metastatic potency. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive form of skin cancer resulting from genetic mutations in melanocytes. Several factors have been considered to be involved in melanoma progression, including genetic alteration, processes of damaged DNA repair, and changes in mechanisms of cell growth and proliferation. Epigenetics is the other factor with a crucial role in melanoma development. Epigenetic changes have become novel targets for treating patients suffering from melanoma. These changes can alter the expression of microRNAs and their interaction with target genes, which involves cell growth, differentiation, or even death. Given these circumstances, we conducted the present review to discuss the melanoma risk factors and represent the current knowledge about the factors related to its etiopathogenesis. Moreover, various epigenetic pathways, which are involved in melanoma progression, treatment, and chemo-resistance, as well as employed epigenetic factors as a solution to the problems, will be discussed in detail. [ABSTRACT FROM AUTHOR]

Plants-based natural compounds are well-identified and recognized chemoprotective agents that can be used for primary and secondary cancer prevention, as they have proven efficacy and fewer side effects. In today's scenario, when cancer cases rapidly increase in developed and developing countries, the anti-cancerous plant-based compounds become highly imperative. Among others, the Asteraceae (Compositae) family's plants are rich in sesquiterpenoid lactones, a subclass of terpenoids with wide structural diversity, and offer unique anti-cancerous effects. These plants are utilized in folk medicine against numerous diseases worldwide. However, these plants are now a part of the modern medical system, with their sesquiterpenoid lactones researched extensively to find more effective and efficient cancer drug regimens. Given the evolving importance of sesquiterpenoid lactones for cancer research, this review comprehensively covers different domains in a spectrum of sesquiterpenoid lactones viz (i) Guaianolides (ii) Pseudoguaianolide (iii) Eudesmanolide (iv) Melampodinin A and (v) Germacrene, from important plants such as Cynara scolymus (globe artichoke), Arnica montana (wolf weeds), Spilanthes acmella, Taraxacum officinale, Melampodium, Solidago spp. The review, therefore, envisages being a helpful resource for the growth of plant-based anti-cancerous drug development. [ABSTRACT FROM AUTHOR]

Background: Mitochondria play critical roles in cellular physiological activity as cellular organelles. Under extracellular stimulation, mitochondria undergo constant fusion and fission to meet different cellular demands. Mitochondrial dynamics, which are involved in mitochondrial fusion and fission, are regulated by specialized proteins and lipids, and their dysregulation causes human diseases, such as cancer. The advanced literature about the crucial role of mitochondrial dynamics in breast cancer is performed. Methods: All related studies were systematically searched through online databases (PubMed, Web of Science, and EMBASE) using keywords (e.g., breast cancer, mitochondrial, fission, and fusion), and these studies were then screened through the preset inclusion and exclusion criteria. Results: Eligible studies (n = 19) were evaluated and discussed in the systematic review. These advanced studies established the roles of mitochondrial fission and fusion of breast cancer in the metabolism, proliferation, survival, and metastasis. Importantly, the manipulating of mitochondrial dynamic is significant for the progresses of breast cancer. Conclusion: Understanding the mechanisms underlying mitochondrial fission and fusion during tumorigenesis is important for improving breast cancer treatments. [ABSTRACT FROM AUTHOR]

The advancement in high-throughput sequencing analysis and the evaluation of chromatin state maps have revealed that eukaryotic cells produce many non-coding transcripts/RNAs. Further, a strong association was observed between some non-coding RNAs and cancer development. The mitogen-activated protein kinases (MAPK) belong to the serine–threonine kinase family and are the primary signaling pathways involved in cell proliferation from the cell surface to the nucleus. They play an important role in various human diseases. A few non-coding RNAs associated with the MAPK signaling pathway play a significant role in the development of several malignancies, including liver cancer. In this review, we summarize the molecular mechanisms and interactions of microRNA, lncRNA, and other non-coding RNAs in the development of liver cancer that are associated with the MAPK signaling pathway. Further, we briefly discuss the therapeutic strategies for liver cancer related to ncRNA and the MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

microRNAs are small non-coding RNAs that regulate several genes post-transcriptionally by complementarity pairing. Since discovery, they have been reported to be involved in a variety of biological functions and pathologies including cancer. In cancer, they can act as a tumor suppressor or oncomiR depending on the cell type. Studies have shown that miRNA-based therapy, either by inhibiting an oncomiR or by inducing a tumor suppressor, is effective in cancer treatment. This review focusses on the role of miRNA in cancer, therapeutic approaches with miRNAs and how they can be effectively delivered into a system. We have also summarized the patents and clinical trials in progress for miRNA therapy. [ABSTRACT FROM AUTHOR]