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The crucial role played by the oncogenic expression of TP53, stemming from mutation or amyloid formation, in various human malignancies has been extensively studied over the past two decades. Interestingly, the potential role of TP53 as a crucial player in modulating immune responses has provided new insight into the field of cancer biology. The loss of p53's transcriptional functions and/or the acquisition of tumorigenic properties can efficiently modulate the recruitment and functions of myeloid and lymphoid cells, ultimately leading to the evasion of immune responses in human tumors. Consequently, the oncogenic nature of the tumor suppressor p53 can dynamically alter the function of immune cells, providing support for tumor progression and metastasis. This review comprehensively explores the dual role of p53 as both the guardian of the genome and an oncogenic driver, especially in the context of regulation of autophagy, apoptosis, the tumor microenvironment, immune cells, innate immunity, and adaptive immune responses. Additionally, the focus of this review centers on how p53 status in the immune response can be harnessed for the development of tailored therapeutic strategies and their potential application in immunotherapy against human malignancies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Cancer biomarkers have revolutionized the field of oncology by providing valuable insights into tumor changes and aiding in screening, diagnosis, prognosis, treatment prediction, and risk assessment. The emergence of "omic" technologies has enabled biomarkers to become reliable and accurate predictors of outcomes during cancer treatment., Content: In this review, we highlight the clinical utility of biomarkers in cancer identification and motivate researchers to establish a personalized/precision approach in oncology. By extending a multidisciplinary technology-based approach, biomarkers offer an alternative to traditional techniques, fulfilling the goal of cancer therapeutics to find a needle in a haystack., Summary and Outlook: We target different forms of cancer to establish a dynamic role of biomarkers in understanding the spectrum of malignancies and their biochemical and molecular characterization, emphasizing their prospective contribution to cancer screening. Biomarkers offer a promising avenue for the early detection of human cancers and the exploration of novel technologies to predict disease severity, facilitating maximum survival and minimum mortality rates. This review provides a comprehensive overview of the potential of biomarkers in oncology and highlights their prospects in advancing cancer diagnosis and treatment., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Aim: Telomerase expression is unique to cancer cells, making it a promising target for therapy. However, a major drawback of telomerase inhibition is that it affects cancer cell proliferation only when telomeres shorten, creating a lag phase post-continuous drug treatment. Acute cytotoxicity of telomerase inhibitors is dependent on their ability to induce DNA damage. p53 senses DNA damage and is the primary effector required for sensitizing cells towards apoptosis., Main Methods: Isogenic p53 +/+ and p53 -/- ovarian cancer cell lines were generated using the CRISPR/Cas9 system and the anti-cancer effect of telomerase inhibitors MST-312 and BIBR1532 were determined. Flow cytometry, real-time PCR, and western blot were performed to study cell cycle, apoptosis, and gene expression., Key Findings: We report that MST-312 exhibits p53-dependent cytotoxicity, while BIBR1532 exhibits p53-independent cytotoxicity. Colony-forming ability also confirms the p53-dependent effect of MST-312. Re-expression of p53 in p53 -/- cells could rescue MST-312 sensitivity. In p53 +/+ cells, MST-312 causes S phase arrest and activation of p53-dependent target genes like anti-apoptosis markers (Fas and Puma) and cell cycle markers (p21 and cyclinB). In p53 -/- cells, MST-312 causes S/G 2 /M arrest. BIBR1532 induces S/G 2 /M phase cell cycle arrest irrespective of p53 status. This correlates with the expression of the DNA damage marker (γ-H2AX). Long-term continuous treatment with MST-312 or BIBR1532 results in p53-independent telomere shortening., Significance: In summary, we demonstrate that acute anti-cancer effects of MST-312 are dependent on p53 expression. Hence, it is important to consider the p53 expression status in cancer cells when selecting and administering telomerase inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The mammalian target of rapamycin (mTOR) is a protein kinase that controls cellular metabolism, catabolism, immune responses, autophagy, survival, proliferation, and migration, to maintain cellular homeostasis. The mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2 (mTORC1/2). mTOR catalyzes the phosphorylation of several critical proteins like AKT, protein kinase C, insulin growth factor receptor (IGF-1R), 4E binding protein 1 (4E-BP1), ribosomal protein S6 kinase (S6K), transcription factor EB (TFEB), sterol-responsive element-binding proteins (SREBPs), Lipin-1, and Unc-51-like autophagy-activating kinases. mTOR signaling plays a central role in regulating translation, lipid synthesis, nucleotide synthesis, biogenesis of lysosomes, nutrient sensing, and growth factor signaling. The emerging pieces of evidence have revealed that the constitutive activation of the mTOR pathway due to mutations/amplification/deletion in either mTOR and its complexes (mTORC1 and mTORC2) or upstream targets is responsible for aging, neurological diseases, and human malignancies. Here, we provide the detailed structure of mTOR, its complexes, and the comprehensive role of upstream regulators, as well as downstream effectors of mTOR signaling cascades in the metabolism, biogenesis of biomolecules, immune responses, and autophagy. Additionally, we summarize the potential of long noncoding RNAs (lncRNAs) as an important modulator of mTOR signaling. Importantly, we have highlighted the potential of mTOR signaling in aging, neurological disorders, human cancers, cancer stem cells, and drug resistance. Here, we discuss the developments for the therapeutic targeting of mTOR signaling with improved anticancer efficacy for the benefit of cancer patients in clinics., (© 2023. West China Hospital, Sichuan University.)

Cancer is one of the leading causes of death worldwide, primarily due to the dearth of efficient therapies that result in long-lasting remission. This is especially true in cases of metastatic cancer where drug resistance causes the disease to recur after treatment. One of the factors contributing to drug resistance, metastasis, and aggressiveness of the cancer is cancer stem cells (CSCs) or tumor-initiating cells. As a result, CSCs have emerged as a potential target for drug development. In the present review, we have examined and highlighted the lncRNAs with their regulatory functions specific to CSCs. Moreover, we have discussed the difficulties and various methods involved in identifying lncRNAs that can play a particular role in regulating and maintaining CSCs. Interestingly, this review only focuses on those lncRNAs with strong functional evidence for CSC specificity and the mechanistic role that allows them to be CSC regulators and be the focus of CSC-specific drug development., Competing Interests: Declaration of Competing Interest All the authors have read and declare they have no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cancer stands in the frontline among leading killers worldwide and the annual mortality rate is expected to reach 16.4 million by 2040. Humans suffer from about 200 different types of cancers and many of them have a small number of approved therapeutic agents. Moreover, several types of major cancers are diagnosed at advanced stages as a result of which the existing therapies have limited efficacy against them and contribute to a dismal prognosis. Therefore, it is essential to develop novel potent anticancer agents to counteract cancer-driven lethality. Natural sources such as bacteria, plants, fungi, and marine microorganisms have been serving as an inexhaustible source of anticancer agents. Notably, over 13,000 natural compounds endowed with different pharmacological properties have been isolated from different bacterial sources. In the present article, we have discussed about the importance of natural products, with special emphasis on bacterial metabolites for cancer therapy. Subsequently, we have comprehensively discussed the various sources, mechanisms of action, toxicity issues, and off-target effects of clinically used anticancer drugs (such as actinomycin D, bleomycin, carfilzomib, doxorubicin, ixabepilone, mitomycin C, pentostatin, rapalogs, and romidepsin) that have been derived from different bacteria. Furthermore, we have also discussed some of the major secondary metabolites (antimycins, chartreusin, elsamicins, geldanamycin, monensin, plicamycin, prodigiosin, rebeccamycin, salinomycin, and salinosporamide) that are currently in the clinical trials or which have demonstrated potent anticancer activity in preclinical models. Besides, we have elaborated on the application of metagenomics in drug discovery and briefly described about anticancer agents (bryostatin 1 and ET-743) identified through the metagenomics approach., Competing Interests: Declaration of Competing Interest There is no conflict of interests to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Plant lectins, a natural source of glycans with a therapeutic potential may lead to the discovery of new targeted therapies. Glycans extracted from plant lectins are known to act as ligands for C-type lectin receptors (CLRs) that are primarily present on immune cells. Plant-derived glycosylated lectins offer diversity in their N-linked oligosaccharide structures that can serve as a unique source of homogenous and heterogenous glycans. Among the plant lectins-derived glycan motifs, Man 9 GlcNAc 2 Asn exhibits high-affinity interactions with CLRs that may resemble glycan motifs of pathogens. Thus, such glycan domains when presented along with antigens complexed with a nanocarrier of choice may bewilder the immune cells and direct antigen cross-presentation - a cytotoxic T lymphocyte immune response mediated by CD8 + T cells. Glycan structure analysis has attracted considerable interest as glycans are looked upon as better therapeutic alternatives than monoclonal antibodies due to their cost-effectiveness, reduced toxicity and side effects, and high specificity. Furthermore, this approach will be useful to understand whether the multivalent glycan presentation on the surface of nanocarriers can overcome the low-affinity lectin-ligand interaction and thereby modulation of CLR-dependent immune response. Besides this, understanding how the heterogeneity of glycan structure impacts the antigen cross-presentation is pivotal to develop alternative targeted therapies. In the present review, we discuss the findings on structural analysis of glycans from natural lectins performed using GlycanBuilder2 - a software tool based on a thorough literature review of natural lectins. Additionally, we discuss how multiple parameters like the orientation of glycan ligands, ligand density, simultaneous targeting of multiple CLRs and design of antigen delivery nanocarriers may influence the CLR targeting efficacy. Integrating this information will eventually set the ground for new generation immunotherapeutic vaccine design for the treatment of various human malignancies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mitochondria, well recognized as the "powerhouse" of cells, are maternally inherited organelles with bacterial ancestry that play essential roles in a myriad of cellular functions. It has become profoundly evident that mitochondria regulate a wide array of cellular and metabolic functions, including biosynthetic metabolism, cell signaling, redox homeostasis, and cell survival. Correspondingly, defects in normal mitochondrial functioning have been implicated in various human malignancies. Cancer development involves the activation of oncogenes, inactivation of tumor suppressor genes, and impairment of apoptotic programs in cells. Mitochondria have been recognized as the site of key metabolic switches for normal cells to acquire a malignant phenotype. This review outlines the role of mitochondria in human malignancies and highlights potential aspects of mitochondrial metabolism that could be targeted for therapeutic development., (Copyright © 2021 Elsevier B.V. All rights reserved.)

H19 long non-coding RNA (lncRNA) has many functions in cancer. Some studies have reported that H19 acts as an oncogene and is involved in cancer progression by activating epithelial-mesenchymal transition (EMT), the cell cycle and angiogenesis via mechanisms like microRNA (miRNA) sponging - the binding to and inhibition of miRNA activity. This makes H19 lncRNA a potential target for cancer therapeutics. However, several conflicting studies have also found that H19 suppresses tumour development. In this review, we shed light on the possible reasons for these conflicting findings. We also summarise the current literature on the applications of H19 lncRNA in cancer therapy in many cancers and explore new avenues for future research. This includes the use of H19 in recombinant vectors, chemoresistance, epigenetic regulation, tumour microenvironment alteration and cancer immunotherapy. The relationship between H19 and the master tumour suppressor gene p53 is also explored. In most studies, H19 knockdown via RNA interference (RNAi) or epigenetic silencing inhibits cancer development. Thus, H19 lncRNA could be a promising target for the development of cancer therapeutics. This warrants further investigations into its translational research to improve cancer therapy outcomes., (Copyright © 2020. Published by Elsevier B.V.)

Based on the high incidence and mortality rates of cancer, its therapy remains one of the most vital challenges in the field of medicine. Consequently, enhancing the efficacy of currently applied treatments and finding novel strategies are of great importance for cancer treatment. Venoms are important sources of a variety of bioactive compounds including salts, small molecules, macromolecules, proteins, and peptides that are defined as toxins. They can exhibit different pharmacological effects, and in recent years, their anti-tumor activities have gained significant attention. Several different compounds are responsible for the anti-tumor activity of venoms, and peptides are one of them. In the present review, we discuss the possible anti-tumor activities of venom peptides by highlighting molecular pathways and mechanisms through which these molecules can act effectively. Venom peptides can induce cell death in cancer cells and can substantially enhance the efficacy of chemotherapy and radiotherapy. Also, the venom peptides can mitigate the migration of cancer cells via suppression of angiogenesis and epithelial-to-mesenchymal transition. Notably, nanoparticles have been applied in enhancing the bioavailability of venom peptides and providing targeted delivery, thereby leading to their elevated anti-tumor activity and potential application for cancer therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Human malignancies are one of the major health-related issues though out the world and anticipated to rise in the future. The development of novel drugs/agents requires a huge amount of cost and time that represents a major challenge for drug discovery. In the last three decades, the number of FDA approved drugs has dropped down and this led to increasing interest in drug reposition or repurposing. The present review focuses on recent concepts and therapeutic opportunities for the utilization of antidiabetics, antibiotics, antifungal, anti-inflammatory, antipsychotic, PDE inhibitors and estrogen receptor antagonist, Antabuse, antiparasitic and cardiovascular agents/drugs as an alternative approach against human malignancies. The repurposing of approved non-cancerous drugs is an effective strategy to develop new therapeutic options for the treatment of cancer patients at an affordable cost in clinics. In the current scenario, most of the countries throughout the globe are unable to meet the medical needs of cancer patients because of the high cost of the available cancerous drugs. Some of these drugs displayed potential anti-cancer activity in preclinic and clinical studies by regulating several key molecular mechanisms and oncogenic pathways in human malignancies. The emerging pieces of evidence indicate that repurposing of drugs is crucial to the faster and cheaper discovery of anti-cancerous drugs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Redox homeostasis is an essential requirement of the biological systems for performing various normal cellular functions including cellular growth, differentiation, senescence, survival and aging in humans. The changes in the basal levels of reactive oxygen species (ROS) are detrimental to cells and often lead to several disease conditions including cardiovascular, neurological, diabetes and cancer. During the last two decades, substantial research has been done which clearly suggests that ROS are essential for the initiation, progression, angiogenesis as well as metastasis of cancer in several ways. During the last two decades, the potential of dysregulated ROS to enhance tumor formation through the activation of various oncogenic signaling pathways, DNA mutations, immune escape, tumor microenvironment, metastasis, angiogenesis and extension of telomere has been discovered. At present, surgery followed by chemotherapy and/or radiotherapy is the major therapeutic modality for treating patients with either early or advanced stages of cancer. However, the majority of patients relapse or did not respond to initial treatment. One of the reasons for recurrence/relapse is the altered levels of ROS in tumor cells as well as in cancer-initiating stem cells. One of the critical issues is targeting the intracellular/extracellular ROS for significant antitumor response and relapse-free survival. Indeed, a large number of FDA-approved anticancer drugs are efficient to eliminate cancer cells and drug resistance by increasing ROS production. Thus, the modulation of oxidative stress response might represent a potential approach to eradicate cancer in combination with FDA-approved chemotherapies, radiotherapies as well as immunotherapies.

Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy., (© 2020 The Author(s).)

Dendritic cells (DCs) present exogenous antigens on major histocompatibility complex (MHC) class I molecules, thereby activating CD8+ T cells, contributing to tumor elimination through a mechanism known as antigen cross-presentation. A variety of factors such as maturation state of DCs, co-stimulatory signals, T-cell microenvironment, antigen internalization routes and adjuvants regulate the process of DC-mediated antigen cross-presentation. Recently, the development of successful cancer immunotherapies may be attributed to the ability of DCs to cross-present tumor antigens. In this review article, we focus on the underlying mechanism of antigen cross-presentation and ways to improve antigen cross-presentation in different DC subsets. We have critically summarized the recent developments in the generation of novel nanovaccines for robust CD8+ T-cell response in cancer. In this context, we have reviewed nanocarriers that have been used for cancer immunotherapeutics based on antigen cross-presentation mechanism. Additionally, we have also expressed our views on the future applications of this mechanism in curing cancer., (© 2019 The Author(s).)