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Aims: This study aimed to evaluate the roles and molecular targets of miRNA-141-3p in the cisplatin sensitivity of osteosarcoma. Background: Osteosarcoma is one of the most common-type bone tumors, occurring mainly in children and adolescents. Cancer cells display dysregulated cellular metabolism, such as the abnormally elevated glutamine metabolism. Objective: Non-coding RNA miRNA-141-3p has been reported to act as a tumor suppressor in osteosarcoma. Currently, the precise molecular mechanisms for the miR- 141-3p-mediated chemosensitivity through regulating glutamine metabolism remain unclear. Methods: We collected thirty paired OS tumors and their adjacent normal tissues. The osteosarcoma cell lines [Saos-2] and normal osteoblast cells, hFOB1.19, were used for in vitro experiments. RT-qPCR and Western blot were applied for gene expression detections. Targets of miR-141-3p were predicted from starBase. The MTT and flow cytometric assays were performed to determine cell growth and apoptosis rates. The cellular glutamine metabolism was monitored by glutamine uptake assay and the glutaminase [GLS] activity assay. Results: We reported that miR-141-3p were significantly downregulated in osteosarcoma tissues and cells. Overexpression of miR-141-3p suppressed OS cell growth and sensitized OS cells to cisplatin. In addition, glutamine metabolism was significantly increased in osteosarcoma. We characterized that GLS played oncogenic roles in osteosarcoma and validated GLS was a direct target of miR-141-3p in OS cells. Rescue experiments consistently demonstrated that miR-141-3p-promoted cisplatin sensitivity was achieved by targeting GLS directly. Conclusion: Overall, our findings revealed new molecular mechanisms of the miR-141- 3p-modulated cisplatin sensitization through targeting the GLS-glutamine metabolism pathway. This study will contribute to developing new therapeutic approaches for the treatments of chemoresistant osteosarcoma.

In this paper, Breast cancer cells grade identify through molecular imaging with chitosan nanoparticles. Breast cancer images with chitosan nanoparticles acquired through SEM camera. However, traditional method of imaging such as CT, Mammogram, and MRI never classifies the cancer grade and never detect cancer cells below 5 mm. The proposed TDyWT based image enhancement of SEM images enhances cancer cells through perspective projection. The perspective projection in cancer cell image enhances cells below 5 mm, preserves boundary, curvature and eliminates cancerous and non cancerous mixed pixels. Furthermore, TDyWT processed image apply with the GLCM parameters for grade classification of cancer cells. From simulation results, proposed TDyWT performs better than traditional algorithms such as DWT and SWT in terms of better visual interpretational and statically parameters.

The active role of bacteria in oncogenesis has long been a topic of debate. Although, it was speculated to be a transmissible cause of cancer as early as the 16th-century, yet the idea about the direct involvement of bacteria in cancer development has only been explored in recent decades. More recently, several studies have uncovered the mechanisms behind the carcinogenic potential of bacteria which are inflammation, immune evasion, pro-carcinogenic metabolite production, DNA damage and genomic instability. On the other side, the recent development on the understanding of tumor microenvironment and technological advancements has turned this enemy into an ally. Studies using bacteria for cancer treatment and detection have shown noticeable effects. Therapeutic abilities of bioengineered live bacteria such as high specificity, selective cytotoxicity to cancer cells, responsiveness to external signals and control after ingestion have helped to overcome the challenges faced by conventional cancer therapies and highlighted the bacterial based therapy as an ideal approach for cancer treatment. In this review, we have made an effort to compile substantial evidence to support the multidimensional role of bacteria in cancer. We have discussed the multifaceted role of bacteria in cancer by highlighting the wide impact of bacteria on different cancer types, their mechanisms of actions in inducing carcinogenicity, followed by the diagnostic and therapeutic potential of bacteria in cancers. Moreover, we have also highlighted the existing gaps in the knowledge of the association between bacteria and cancer as well as the limitation and advantage of bacteria-based therapies in cancer. A better understanding of these multidimensional roles of bacteria in cancer can open up the new doorways to develop early detection strategies, prevent cancer, and develop therapeutic tactics to cure this devastating disease.

Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC.

Abstract: Cancer is an important health issue worldwide. Cancer therapy is multifaceted, and drug resistance is still the major limiting factor in the treatment of patients with this disease. Although the mechanisms of anticancer drug resistance have been broadly investigated, a massive biological signal pathway of Non-coding RNAs (ncRNAs) involved in this process has not been completely understood. Long noncoding RNAs (lncRNAs) are a kind of transcripts with a minimum length of 200 nucleotides in size, which have a limited potential for coding proteins. The roles of these RNA molecules have been evaluated in relation to several pathological processes, including tumor formation and progression. Increasing evidence has recently reported that non-coding RNAs (ncRNAs), particularly long non-coding RNAs, have significant roles in many cellular and genomic processes, and because of their potential in regulation specific genes, they are also involved in drug resistance. In this review, we review the literature on the features of lncRNA, their regulation roles in the gene expression related to chemo resistance, and the potential of these RNAs as targeted therapies for personalized treatment in cancers.

Objective: To investigate the effect of miR-146a on the sensitivity of breast cancer cells to paclitaxel (PTX). Materials and Methods: The mRNA expressions of miR-146a in normal breast cancer cells...

The acquisition of DNA damage is an early driving event in tumorigenesis. Premalignant lesions show activated DNA damage responses and inactivation of DNA damage checkpoints promotes malignant transformation. However, DNA damage is also a targetable vulnerability in cancer cells. This requires a detailed understanding of the cellular and molecular mechanisms governing DNA integrity. Here, we review current work on DNA damage in tumorigenesis. We discuss DNA double strand break repair, how repair pathways contribute to tumorigenesis, and how double strand breaks are linked to the tumor microenvironment. Next, we discuss the role of oncogenes in promoting DNA damage through replication stress. Finally, we discuss our current understanding on DNA damage in micronuclei and discuss therapies targeting these DNA damage pathways.

Background: Cancer, a malignant tumor, is caused by the failure of the mechanism that controls cell growth and proliferation. Late clinical symptoms often manifest as lumps, pain, ulcers, and bleeding. Systemic symptoms include weight loss, fatigue, and loss of appetite. It is a major disease that threatens human life and health. How to treat cancer is a long-standing problem that needs to be overcome in the history of medicine. Discussion: In this study, we systematically review the cancer treatment evolution from traditional methods to novel approaches that include immunotherapy, nanotherapy, stem cell theapy, and gene therapy. We provide the latest review of the application status, clinical trials, and development prospects of mesenchymal stem cells and gene therapy for cancer, as well as their integration in cancer treatment. Mesenchymal stem cells are effective carriers carrying genes and provide new clinical ideas for tumor treatment. Methods: Traditional tumor treatment methods are poorly targeted, and the side effects of treatment seriously damage the physical and mental health of patients. In recent years, with the advancement of medical science and technology, the research on gene combined with mesenchymal stem cells to treat tumors has been intensified. Mesenchymal stem cells carry genes to target cancer cells, which can achieve better therapeutic effects. Conclusion: This review focuses on the current status, application prospects, and challenges of mesenchymal stem cell combined gene therapy for cancer and provides new ideas for clinical research.

Introduction There are more than two dozen bispecific antibodies (BsAbs) in development with a variety of designs which are relevant to breast cancer. The field of BsAbs for breast cancer includes agents that co-direct immune recognition of the cancer cell, target unique cancer antigens, and target the microenvironment. BsAbs are being developed for use as antibody-drug conjugates and as homing signals for engineered T-cells. Areas covered This review covers potential targets for bispecific antibodies, agents in pre-clinical development, agents in clinical trials, combinatorial therapies, and future directions. Expert opinion There is no BsAb approval expected for breast cancer in the near term, but late-stage trials are underway. Future BsAb roles in breast cancer are possible given unmet needs in estrogen receptor+ disease, residual disease, and de-escalating chemotherapy use. The HER2+ space shows hints of success for BsAbs, but is already crowded. Areas of unmet need still exist.

Leukemias and lymphomas acquire the capacity for unrestrained cell growth and proliferation in conjunction with loss of responsiveness to molecular programs that promote terminal differentiation. Malignant cells generate the building blocks required for rapid cell division through both increased acquisition of nutrients from the environment and reprogrammed intermediary metabolism to shunt these molecules into producing the protein, lipids, and nucleic acids that comprise cell biomass. These accelerated metabolic processes require energy in the form of ATP and reducing equivalents in the form of NADPH, which power biosynthetic reactions and buffer oxidative stress encountered by the metabolically active cancer cell. Cancer-associated metabolic alterations can also promote accumulation or depletion of specific metabolites that directly regulate cell fate and function, thereby coupling metabolic reprogramming to dedifferentiation and stemness. This review will focus on the mechanisms by which leukemia and lymphoma cells rewire cellular metabolism to support: (1) bioenergetics, (2) biomass accumulation, (3) redox balance, and (4) differentiation blockade. We will further highlight examples of how specific pathways of leukemia and lymphoma metabolism confer therapeutic vulnerabilities that can be targeted to inhibit growth or promote differentiation.

Interaction of a tumor with its microenvironment is an emerging field of investigation, and the crosstalk between cancer cells and the extracellular matrix is of particular interest, since cancer patients with abundant and stiff extracellular matrices display a poorer prognosis. At the post-juvenile stage, the extracellular matrix plays predominantly a structural role by providing support to cells and tissues; however, during development, matrix proteins exert a plethora of diverse signals to guide the movement and determine the fate of pluripotent cells. Taking a closer look at the communication between the extracellular matrix and cells of a developing body may bring new insights into cancer biology and identify cancer weaknesses. This review discusses parallels between the extracellular matrix roles during development and tumor growth.

Noncoding RNAs (ncRNAs) regulation of various diseases including cancer has been extensively studied. Reactive oxidative species (ROS) elevated by oxidative stress are associated with cancer progression and drug resistance, while autophagy serves as an ROS scavenger in cancer cells. However, the regulatory effects of ncRNAs on autophagy and ROS in various cancer cells remains complex. Here, we explore how currently investigated ncRNAs, mainly miRNAs and lncRNAs, are involved in ROS production through modulating antioxidant genes. The regulatory effects of miRNAs and lncRNAs on autophagy-related (ATG) proteins to control autophagy activity in cancer cells are discussed. Moreover, differential expression of ncRNAs in tumor and normal tissues of cancer patients are further analyzed using The Cancer Genome Atlas (TCGA) database. This review hypothesizes links between ATG genes- or antioxidant genes-modulated ncRNAs and ROS production, which might result in tumorigenesis, malignancy, and cancer recurrence. A better understanding of the regulation of ROS and autophagy by ncRNAs might advance the use of ncRNAs as diagnostic and prognostic markers as well as therapeutic targets in cancer therapy.

Background: Long noncoding RNA small nucleolar RNA host gene 3 (SNHG3) is related to the proliferation and metastasis of cancer cells. This study aims to reveal the role of SNHG3 in prostate cancer...

The world-wide rate of incidence of cancer disease has been only modestly contested by the past and current preventive and interventional strategies. Hence, the global effort towards novel ideas to contain the disease still continues. Constituents of human diets have in recent years emerged as key regulators of carcinogenesis, with studies reporting their inhibitory potential against all the three stages vis-a-vis initiation, promotion and progression. Unlike drugs which usually act on single targets, these dietary factors have an advantage of multi-targeted effects and pleiotropic action mechanisms, which are effective against cancer that manifest as a micro-evolutionary and multi-factorial disease. Since most of the cellular targets have been identified and their consumption considered relatively safe, these diet-derived agents often appear as molecules of interest in repurposing strategies. Currently, many of these molecules are being investigated for their ability to influence the aberrant alterations in cell's epigenome for epigenetic therapy against cancer. Targeting the epigenetic regulators is a new paradigm in cancer chemoprevention which acts to reverse the warped-up epigenetic alterations in a cancer cell, thereby directing it towards a normal phenotype. In this review, we discuss the significance of dietary factors and natural products as chemopreventive agents. Further, we corroborate the experimental evidence from existing literature, reflecting the ability of a series of such molecules to act as epigenetic modifiers in cancer cells, by interfering with molecular events that map the epigenetic imprints such as DNA methylation, histone acetylation and non-coding RNA mediated gene regulation.

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.

Both genetic and epigenetic mechanisms intimately regulate cancer development and chemoresistance. Different genetic alterations are observed in multiple genes, and most are irreversible. Aside from genetic alterations, epigenetic alterations play a crucial role in cancer. The reversible nature of epigenetic modifications makes them an attractive target for cancer prevention and therapy. Specific epigenetic alteration is also being investigated as a potential biomarker in multiple cancers. c-MYC is one of the most important transcription factors that are centrally implicated in multiple types of cancer cells reprogramming, proliferation, and chemoresistance. c-MYC shows not only genetic alterations but epigenetic changes in multiple cancers. It has been observed that epigenome aberrations can reversibly alter the expression of c-MYC, both transcriptional and translational levels. Understanding the underlying mechanism of the epigenetic alterations of c-MYC, that has its role in multiple levels of cancer pathogenesis, can give a better understanding of various unresolved questions regarding cancer. Recently, some researchers reported that targeting the epigenetic modifiers of c-MYC can successfully inhibit cancer cell proliferation, sensitize the chemoresistant cells, and increase the patient survival rate. As c-MYC is an important transcription factor, epigenetic therapy might be one of the best alternatives for the conventional therapies that assumes the "one-size-fits-all" role. It can also increase the precision of targeting and enhance the effectiveness of treatments among various cancer subtypes. In this review, we highlighted the role of epigenetically modified c-MYC in cancer cell reprogramming, progression, and chemoresistance. We also summarize the potential therapeutic approaches to target these modifications for the prevention of cancer development and chemoresistant phenotypes.

The invasion of cancer cells into the surrounding tissues is one of the hallmarks of cancer. However, a precise quantitative understanding of the spatiotemporal patterns of cancer cell migration and invasion still remains elusive. A promising approach to investigate these patterns are 3D cell cultures, which provide more realistic models of cancer growth compared to conventional 2D monolayers. Quantifying the spatial distribution of cells in these 3D cultures yields great promise for understanding the spatiotemporal progression of cancer. In the present study, we present an image processing and segmentation pipeline for the detection of 3D GFP-fluorescent Triple-Negative Breast Cancer cell nuclei, and we perform quantitative analysis of the formed spatial patterns and their temporal evolution. The performance of the proposed pipeline was evaluated using experimental 3D cell culture data, and was found to be comparable to manual segmentation, outperforming four alternative automated methods. The spatiotemporal statistical analysis of the detected distributions of nuclei revealed transient, non-random spatial distributions that consisted of clustered patterns across a wide range of neighbourhood distances, as well as dispersion for larger distances. Overall, the implementation of the proposed framework revealed the spatial organization of cellular nuclei with improved accuracy, providing insights into the 3 dimensional inter-cellular organization and its progression through time.

Background Chemotherapy is a first-line treatment for advanced and metastatic bladder cancer, but the unsatisfactory objective response rate to this treatment yields poor 5-year patient survival. Only PD-1/PD-L1-based immune checkpoint inhibitors, FGFR3 inhibitors and antibody-drug conjugates are approved by the FDA to be used in bladder cancer, mainly for platinum-refractory or platinum-ineligible locally advanced or metastatic urothelial carcinoma. Emerging studies indicate that the combination of targeted therapy and chemotherapy shows better efficacy than targeted therapy or chemotherapy alone. Newly identified targets in cancer cells and various functions of the tumour microenvironment have spawned novel agents and regimens, which give impetus to sensitizing chemotherapy in the bladder cancer setting. Aim of Review: This review aims to present the current evidence for potentiating the efficacy of chemotherapy in bladder cancer. We focus on combining chemotherapy with other treatments as follows: targeted therapy, including immunotherapy and antibody-drug conjugates in clinic; novel targeted drugs and nanoparticles in preclinical models and potential targets that may contribute to chemosensitivity in future clinical practice. The prospect of precision therapy is also discussed in bladder cancer. Key Scientific Concepts of Review: Combining chemotherapy drugs with immune checkpoint inhibitors, antibody-drug conjugates and VEGF inhibitors potentially elevates the response rate and survival. Novel targets, including cancer stem cells, DNA damage repair, antiapoptosis, drug metabolism and the tumour microenvironment, contribute to chemosensitization. Gene alteration-based drug selection and patient-derived xenograft- and organoid-based drug validation are the future for precision therapy.

Background Hepatocellular carcinoma (HCC) is recognized as a leading cause of cancer-associated fatality worldwide. Our study here aimed to probe the mechanism by which exosomes secreted by CSQT-2, an HCC cell line, affected the progression of HCC. Methods Exosomes were extracted from CSQT-2 cells. Colony formation, Transwell, sphere formation and flow cytometric analyses were applied to assess cell biological activities. Microarray analysis detected the change of microRNA (miRNA) expression after exosome treatment, followed by RT-qPCR validation. Luciferase reporter was applied to detect the binding between SIK1 and miR-25. Xenograft studies in nude mice manifested tumor growth and metastatic ability of miR-25 and SIK1. Results The exosome treatment enhanced cell malignant phenotype in vitro and tumor growth and liver and lung metastases in vivo. The exosomes elevated miR-25 expression in HCC cells. miR-25 targeted SIK1 which was decreased in the exosomes-treated cells. miR-25 inhibitor reduced cell malignant phenotype and attenuated tumorigenesis and metastasis in vivo. SIK1 silencing reversed the effect of miR-25 inhibitor. The exosome treatment potentiated the Wnt/β-catenin pathway in cells, whereas miR-25 inhibitor blunted the pathway activity. Conclusion MiR-25 shuttled through CSQT-2-derived exosomes promoted the development of HCC by reducing SIK1 expression and potentiating the Wnt/β-catenin pathway.

Abstract: Brain tissue is known to have elevated citrate levels, necessary to regulate ion chelation, neuron excitability, and are also necessary for the supply of necessary energy substrates to neurons. Importantly, citrate also acts as a central substrate in cancer metabolism. Recent studies have shown that extracellular citrate levels in the brain undergo significant changes during tumor development and may play a dual role in tumor progression, as well as cancer cell aggressiveness. In the present article, we review available literature describing changes of citrate levels in brain tissue, blood, and cerebrospinal fluid, as well as intracellular alterations during tumor development before and after metastatic progression. Based on the available literature and our recent findings, we hypothesize that changes in extracellular citrate levels may be related to the increased consumption of this metabolite by cancer cells. Interestingly, cancerassociated cells, including reactive astrocytes, might be a source of citrate. Extracellular citrate uptake mechanisms, as well as potential citrate synthesis and release by surrounding stroma, could provide novel targets for anti-cancer treatments of primary brain tumors and brain metastases.

Brain tumors remain one of the most difficult tumors to treat and, depending on the diagnosis, have a poor prognosis. Of brain tumors, glioblastoma (GBM) is the most common malignant glioma and has a dismal prognosis, with only about 5% of patients alive five years after diagnosis. While advances in targeted therapies and immunotherapies are rapidly improving outcomes in a variety of other cancers, the standard of care for GBM has largely remained unaltered since 2005. There are many well-studied challenges that are either unique to brain tumors (i.e., blood-brain barrier and immunosuppressive environment) or amplified within GBM (i.e., tumor heterogeneity at the cellular and molecular levels, plasticity, and cancer stem cells) that make this disease particularly difficult to treat. While we touch on all these concepts, the focus of this review is to discuss the immense inter- and intra-tumoral heterogeneity and advances in our understanding of tumor cell plasticity and epigenetics in GBM. With each improvement in technology, our understanding of the complexity of tumoral heterogeneity and plasticity improves and we gain more clarity on the causes underlying previous therapeutic failures. However, these advances are unlocking new therapeutic opportunities that scientists and physicians are currently exploiting and have the potential for new breakthroughs.

Glioblastoma (GBM) and other malignant tumours consist of heterogeneous cancer cells, including GBM-initiating cells (GICs). This heterogeneity is likely to arise from the following: different sets of genetic mutations and epigenetic modifications, which GICs gain in the transformation process; differences in cells of origin, such as stem cells, precursor cells or differentiated cells; and the cancer microenvironment, in which GICs communicate with neural cells, endothelial cells and immune cells. Furthermore, considering that various types of GICs can be generated at different time points of the transformation process, GBM very likely consists of heterogeneous GICs and their progeny. Because cancer cell heterogeneity is responsible for therapy resistance, it is crucial to develop methods of reducing such heterogeneity. Here, I summarize how GIC heterogeneity is generated in the transformation process and present how cell heterogeneity in cancer can be addressed based on recent findings.

Cancer initiating/ stem cells (CSCs) undergo self-renewal and differentiation that contributes to tumor initiation, recurrence and metastasis in colorectal cancer (CRC). Targeting of colorectal cancer stem cells (CCSCs) holds significant promise in eradicating cancer cells and ultimately curing patients with cancer. In this review, we will introduce the current progress of CCSC studies, including the specific surface markers of CCSCs, the intrinsic signaling pathways that regulate the stemness and differentiation characteristics of CCSCs, and the tumor organoid model for CCSC research. We will focus on how these studies will lead to the progress in targeting specific surface markers or signaling pathways on CCSCs by monoclonal antibodies, or by natural or synthetic compounds, or by immunotherapy. As CSCs are highly heterogeneous and plastic, we suggest that combinatory approaches that target the stemness network may represent an important strategy for eradicating cancers.

Cancer, a challenging medical problem, affects millions of people around the world. Cancer cell resistance is one of the main drawbacks in the complete prosperity of even more sophisticated therapies. Pore-forming peptides (PFPs), a group of natural defense system proteins are used by nearly all living organisms as anti-bacterial and anti-- fungal agents, and could also be regarded as novel tumoricidal peptides. PFPs approach entails using soluble peptides by assembling them mainly on the target cell membrane and forming potential death-causing pores. Physical damage induction by natural PFPs or their synthetic derivatives could conquer the resistance mechanisms of tumor cells. Given that peptide drugs involve a significant proportion of the pharmaceutical market primarily because of easy synthesis and safety, evaluating this nature provided a model system as a group of anticancer peptides seems a valuable approach. Here, the mode of action of PFPs and their anticancer mechanism are highlighted, followed by addressing the anticancer studies using PFPs from different sources along with various strategies applied to obtain selective action of PFPs against cancer cells. Challenges and future perspectives of these promising bioactive molecules in cancer treatment are also provided.

Polyploid giant cancer cells (PGCCs) are a commonly observed histological feature of human tumors and are particularly prominent in late stage and drug resistant cancers. The chromosomal duplication conferred by their aneuploidy gives rise to DNA damage resistance and complex tumor cell karyotypes, a driving factor in chemotherapy resistance and disease relapse. Furthermore, PGCCs also exhibit key cytoskeletal features that give rise to a distinct biophysical phenotype, including increased density of polymerized actin and vimentin intermediate filaments, nuclear and cytoskeletal stiffening, increased traction force, and migratory persistence. Despite recent research highlighting the role PGCCs play in cancer progression, this population of tumor cells remains poorly characterized in terms of their biophysical properties. In this review, we will discuss the various aspects of their biomolecular phenotype, such as increased stemness as well as a mixed EMT signature. These features have been extensively associated with tumorigenesis and recurrence, and aggressive cancers. Additionally, we will also examine the distinct PGCC cytoskeletal features of actin and filamentous vimentin. Specifically, how the differential organization of these networks serve to support their increased size and drive migratory persistence. These findings could shed light on potential therapeutic strategies that allow for specific elimination or mitigation of the invasive potential of these polyploid cancer cells. Lastly, we will examine how the biophysical and molecular phenotype of PGCCs combine to tip the scale in favor of promoting cancer progression, presenting an important target in the clinical treatment of cancer.

Nuclear factor κB (NF-κB) is a ubiquitous regulator of the signalome and is indispensable for various biological cell functions. NF-κB consists of five transcription factors that execute both cytoplasmic and nuclear signaling processes in cells. NF-κB is the only signaling molecule that governs both pro- and anti-apoptotic, and pro- and anti-inflammatory responses. This is due to the canonical and non-canonical components of the NF-κB signaling pathway. Together, these pathways orchestrate cancer-related inflammation, hyperplasia, neoplasia, and metastasis. Non-canonical NF-κB pathways are particularly involved in the chemoresistance of cancer cells. In view of its pivotal role in cancer progression, NF-κB represents a potentially significant therapeutic target for modifying tumor cell behavior. Several phytochemicals are known to modulate NF-κB pathways through the stabilization of its inhibitor, IκB by inhibiting the phosphorylation and ubiquitination thereof. Several natural pharmacophores are known to inhibit the nuclear translocation of NF-κB and associated pro-inflammatory responses and cell survival pathways. In view of this, and the high degree of specificity exhibited by various phytochemicals for the NF-κB component, we herein present an in-depth overview of these phytochemicals and discuss their mode of interaction with the NF-κB signaling pathways for controlling fate of tumor cells for cancer-directed interventions.

Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associated with mitigation strategies against environmental change, severe stress, or the lack of nutrients. Our comparison of the mechanisms for polyploidization in other organisms and non-transformed tissues suggest that cancer cells draw from a conserved program for their survival, utilizing whole genome doubling and pausing proliferation to survive stress. These polyaneuploid cancer cells (PACCs) are the source of therapeutic resistance, responsible for cancer recurrence and, ultimately, cancer lethality.

We have presented an in vitro trackable model system, atavistic induced from conservation in our genome, which strongly is applicable to tumorigenesis start and evolution. The inducing factor was death signals to proliferating normal human cells (primary cell strains), which respon-ded by a special type of tetraploidization, chromosomes with 4-chromatids (diplochromosomes, earlier described in cancer cells). The response included cell cycle stress, which prolonged S-period with result of mitotic slippage process, forming the special 4n cells by re-replication of diploid cells, which showed cell division capability to unexpected, genome reduced diploid cells which remarkably, showed fitness gain. This unique response through cell cycle stress and mitotic slippage process was further discovered to be linked to a rather special characteristic of the, 4n nucleus. The nucleus turned, self-inflicted, 90° perpendicular to the cell's cytoskeleton axis, importantly, before the special 4n-division system produced genome reduce diploid cells, we call "first cells", because of fitness gain. These 2n cells also showed the nuclear dependent 90° turn, which in both cases was associated with cells gaining cell shape changes, herein illustrated from normal fibroblastic cells changing to roundness cells, indistinguishable from todays' diagnostic cancer cell morphology. This 3-D ball-like cell shape, in metastasis, sque-ezing in and out between (?) endothelial cells in the lining of blood veins during disbursement, would be advantageous.

Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.

The completion-of-tumor hypothesis involved in the dynamic interplay between the initiating oncogenic event and progression is essential to better recognize the foundational framework of tumors. Here we review and extend the gametogenesis-related hypothesis of tumors, because high embryonic/germ cell traits are common in tumors. The century-old gametogenesis-related hypothesis of tumors postulated that tumors arise from displaced/activated trophoblasts, displaced (lost) germ cells, and the reprogramming/reactivation of gametogenic program in somatic cells. Early primordial germ cells (PGCs), embryonic stem (ES) cells, embryonic germ cells (EGCs), and pre-implantation embryos at the stage from two-cell stage to blastocysts originating from fertilization or parthenogenesis have the potential to develop teratomas/teratocarcinomas. In addition, the teratomas/teratocarcinomas/germ cells occur in gonads and extra-gonads. Undoubtedly, the findings provide strong support for the hypothesis. However, it was thought that these tumor types were an exception rather than verification. In fact, there are extensive similarities between somatic tumor types and embryonic/germ cell development, such as antigens, migration, invasion, and immune escape. It was documented that embryonic/germ cell genes play crucial roles in tumor behaviors, e.g. tumor initiation and metastasis. Of note, embryonic/germ cell-like tumor cells at different developmental stages including PGC and oocyte to the early embryo-like stage were identified in diverse tumor types by our group. These embryonic/germ cell-like cancer cells resemble the natural embryonic/germ cells in morphology, gene expression, the capability of teratoma formation, and the ability to undergo the process of oocyte maturation and parthenogenesis. These embryonic/germ cell-like cancer cells are derived from somatic cells and contribute to tumor formation, metastasis, and drug resistance, establishing asexual meiotic embryonic life cycle. p53 inhibits the reactivation of embryonic/germ cell state in somatic cells and oocyte-like cell maturation. Based on earlier and our recent studies, we propose a novel model to complete the gametogenesis-related hypothesis of tumors, which can be applied to certain somatic tumors. That is, tumors tend to establish a somatic asexual meiotic embryonic cycle through the activation of somatic female gametogenesis and parthenogenesis in somatic tumor cells during the tumor progression, thus passing on corresponding embryonic/germ cell traits leading to the malignant behaviors and enhancing the cells' independence. This concept may be instrumental to better understand the nature and evolution of tumors. We rationalize that targeting the key events of somatic pregnancy is likely a better therapeutic strategy for cancer treatment than directly targeting cell mitotic proliferation, especially for those tumors with p53 inactivation.

Background: Gastric Cancer (GC) is the fifth most common malignancy tumor and the third cause of cancer-related death around the world. Immune checkpoint inhibitors (ICIs) such as programmed cell death-1 (PD-1) antibodies play an active role in tumor therapy. A recent study reveals that Wnt/β-catenin signaling pathway is negatively correlated with T-cell infiltration in tumor microenvironment (TME), thereby influencing the therapeutic efficacy of PD-1 antibody. Objective: In this study, we aimed to uncover the relationship of Wnt/β-catenin pathway to CD8+ T cell activity as well as its effect on anti-PD-1 therapeutic efficacy in GC. Methods and Results: We first collected clinical samples and went through an immunohistochemical analysis and found that a high β-catenin expression in GC tissues was often associated with a significant absence of CD8+ T-cell infiltration. In addition, our data further indicated that disruption of the Wnt/β-catenin pathway in GC cells inhibited their migratory and invasive ability. Meanwhile, enhanced sensitivity of GC cells to PD-1 blockade therapy was evident by decreased Jurkat cell apoptosis rate and increased GC cell apoptosis rate in a tumor and Jurkat cells co-culture system with the presence of Wnt/β-catenin pathway inhibition. Conclusion: Collectively, these findings indicated Wnt/β-catenin pathway may play a significant role in modulating the activity of Jurkat cells and downregulation of Wnt/β-catenin may enhance the sensitivity of GC cells to PD-1 antibody in vitro. This result further indicated that β-catenin and PD-1 targeted inhibition might become a potential and effective therapy for GC patients.

Slow-cycling/dormant cancer cells (SCCs) have pivotal roles in driving cancer relapse and drug resistance. A mechanistic explanation for cancer cell dormancy and therapeutic strategies targeting SCCs are necessary to improve patient prognosis, but are limited because of technical challenges to obtaining SCCs. Here, by applying proliferation-sensitive dyes and chemotherapeutics to non-small cell lung cancer (NSCLC) cell lines and patient-derived xenografts, we identified a distinct SCC subpopulation that resembled SCCs in patient tumors. These SCCs displayed major dormancy-like phenotypes and high survival capacity under hostile microenvironments through transcriptional upregulation of regulator of G protein signaling 2 (RGS2). Database analysis revealed RGS2 as a biomarker of retarded proliferation and poor prognosis in NSCLC. We showed that RGS2 caused prolonged translational arrest in SCCs through persistent eukaryotic initiation factor 2 (eIF2α) phosphorylation via proteasome-mediated degradation of activating transcription factor 4 (ATF4). Translational activation through RGS2 antagonism or the use of phosphodiesterase 5 inhibitors, including sildenafil (Viagra), promoted ER stress-induced apoptosis in SCCs in vitro and in vivo under stressed conditions, such as those induced by chemotherapy. Our results suggest that a low-dose chemotherapy and translation-instigating pharmacological intervention in combination is an effective strategy to prevent tumor progression in NSCLC patients after rigorous chemotherapy.

Resistance to chemotherapy is a leading cause of treatment failure. Drug-resistance mechanisms involve mutations in specific proteins or changes in their expression levels. It is commonly understood that resistance mutations happen randomly prior to treatment and are selected during the treatment. However, selection of drug-resistant mutants in culture could be achieved by multiple drug exposures of cloned genetically identical cells, and thus cannot result from selection of pre-existent mutations. Accordingly, adaptation must involve generation of mutations de-novo upon drug treatment. Here we explored the origin of resistance mutations to a widely used Top1 inhibitor irinotecan, which triggers DNA breaks, causing cytotoxicity. Resistance mechanism involved gradual accumulation of recurrent mutations in non-coding regions of DNA at Top1-cleavage sites. Surprisingly, cancer cells had higher number of such sites than reference genome, which may define their increased sensitivity to irinotecan. Homologous recombination repair of DNA double strand breaks at these sites following initial drug exposures gradually reverted cleavage-sensitive “cancer” sequences back to cleavage-resistant “normal” sequences. These mutations reduced generation of DNA breaks upon subsequent exposures, thus gradually increasing the drug resistance. Together, large target size for mutations and their Top1-guided generation lead to their gradual and rapid accumulation, synergistically accelerating development of resistance.Abstract Figure

The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID) mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy) to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy). In parallel, in situ end-labelling (ISEL) staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

As an evolutionarily conserved DNA-sensing machinery in innate immunity, the cGAS-STING pathway has been reported to play an important role in immune surveillance and tumor suppression. Recent evidence suggests an intriguing tumor- and metastasis-promoting effect of this signaling pathway, either in a cancer cell-autonomous or a cancer cell-nonautonomous, bystander cell-mediated manner. Here, we show a new face of cGAS-STING signaling whose activation in a cancer-cell-autonomous response manner confers drug resistance. Targeted or conventional chemotherapy drug treatment induced cancer cell cytosolic DNA accumulation and triggered subsequent cGAS-STING signaling activation in cancer cell lines and the human cell-derived xenograft tumors. This activation promoted an acquisition and maintenance of drug resistance which was prevented and overcome in vitro and in vivo by blockade of STING signaling. This finding highlights a new face of cGAS-STING signaling and an ability of cancer cells to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress and warrants a caution in combining STING agonist with targeted or conventional chemotherapy drug treatment, a strategy prevailing in current clinical trials.Statement of significancecGAS-STING signaling has long been recognized as playing a key role in triggering antitumor immunity. We reveal a new face of cGAS-STING signaling and an ability of cancer cells autonomously to hijack the evolutionarily conserved inflammatory signaling to counteract drug stress.

Lipid-based nanoparticles as drug delivery carriers have been mainly used for delivery of anti-cancer therapeutic agents. Lipid-based nanoparticles, due to their smaller particle size and similarity to cell membranes, are readily internalized into cancer cells. Interestingly, cancer cells also overexpress receptors for specific ligands including folic acid, hyaluronic acid, and transferrin on their surface. This allows the use of these ligands for surface modification of the lipid-based nanoparticle. These modifications then allow the specific recognition of these ligand-coated nanoparticles by their receptors on cancer cells allowing the targeted gradual intracellular accumulation of the functionalized nanoplatforms. These interactions could eventually enhance the internalization of desired drugs via increasing ligand-receptor mediated cellular uptake of the nanoplatforms. The cellular internalization of the nanoplatforms also varies and depends on their physicochemical properties including particle size, zeta potential, and shape. The cellular uptake is also influenced by the types of ligand internalization pathway utilized by cells such as phagocytosis, macropinocytosis, and multiple endocytosis pathways. In this review, we will classify and discuss lipid based nanoparticles engineered to express specific ligands, and are recognized by their receptors on cancer cell, and their cellular internalization pathways. Moreover, the intracellular fate of nanoparticles decorated with specific ligands and the best internalization pathways (caveolae mediated endocytosis) for safe cargo delivery will be discussed.

Background: Cancer is the world’s third deadliest disease. Despite the availability of numerous treatments, researchers are focusing on the development of new drugs with no resistance and toxicity issues. Many newly synthesized drugs fail to reach clinical trials due to poor pharmacokinetic properties. Therefore, there is an imperative requisite to expand novel anticancer agents with in vivo efficacy. Objective: This review emphasizes synthetic methods, contemporary strategies used for the inclusion of oxazole moiety, mechanistic targets, along with comprehensive structure-activity relationship studies to provide perspective into the rational design of highly efficient oxazole-based anticancer drugs. Methods: Literature related to oxazole derivatives engaged in cancer research is reviewed. This article gives a detailed account of synthetic strategies, targets of oxazole in cancer, including STAT3, Microtubules, G-quadruplex, DNA topoisomerases, DNA damage, protein kinases, miscellaneous targets, in vitro studies, and some SAR studies. Results: Oxazole derivatives possess potent anticancer activity by inhibiting novel targets such as STAT3 and Gquadruplex. Oxazoles also inhibit tubulin protein to induce apoptosis in cancer cells. Some other targets such as DNA topoisomerase enzyme, protein kinases, and miscellaneous targets including Cdc25, mitochondrial enzymes, HDAC, LSD1, HPV E2 TAD, NQO1, Aromatase, BCl-6, Estrogen receptor, GRP-78, and Keap-Nrf2 pathway are inhibited by oxazole derivatives. Many derivatives showed excellent potencies on various cancer cell lines with IC50 values in nanomolar concentrations. Conclusion: Oxazole is a five-membered heterocycle, with oxygen and nitrogen at 1 and 3 positions, respectively. It is often combined with other pharmacophores in the expansion of novel anticancer drugs. In summary, oxazole is a promising entity to develop new anticancer drugs.

Background: Breast cancer is the leading cause of cancer death in women. The current methods of chemotherapy for breast cancer generally have strong adverse reactions and drug resistance. Therefore, the discovery of novel anti-breast cancer lead compounds is urgently needed. Objective: This study aimed to design and synthesize a series of 2-alkyl substituted fluorinated genistein analogues and evaluate their anti-breast cancer activity. Methods: Target compounds were obtained in a multistep reaction synthesis. The anti-tumor activity of compounds I-1~I-35 was evaluated with MCF-7, MDA-MB-231, MDA-MB-435, and MCF-10A cell lines in vitro, with tamoxifen as the positive control. Molecular docking was used to study the interaction between the synthesized compounds and PI3K-gamma. Results: A series of 2-alkyl substituted fluorinated genistein analogues was designed, synthesized, and screened for their bioactivity. Most of the compounds displayed better selectivity toward breast cancer cell lines as compared to tamoxifen. Among these analogues, I-2, I-3, I-4, I-9, I-15, and I-17 have the strongest selective inhibition of breast cancer cells. Compounds I-10, I-13, I-15, I-17, and I- 33 were found to have significant inhibitory effects on breast cancer cells. Molecular docking studies have shown that these compounds may act as PI3Kγ inhibitors and may further exhibit anti-breast cancer effects. Conclusion: Most of the newly synthesized compounds could highly, selectively inhibit breast cancer cell lines. The experimental results indicate that the synthesized analogs may also have obvious selective inhibitory effects on other malignant proliferation cancer cells.

Background: Chronic inflammation plays a crucial role in the initiation, promotion, and invasion of tumors, and thus the antiproliferative effects of numerous anti-inflammatory drugs have been frequently reported in the literature. Upregulation of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) has been linked to various human cancers, including breast cancer. Objective: This research aims to investigate the antiproliferative activity of different Non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 selective and non-selective agents, against various breast cancer cell lines and to elucidate possible molecular pathways involved in their activity. Methods: The antiproliferative and combined effects of NSAIDs with raloxifene were evaluated by MTT assay. Cell migration was assessed using a wound-healing assay. The mechanism of cell death was determined using the Annexin V-FITC/ propidium iodide staining flow cytometry method. A mass spectrometry-based targeted metabolomics approach was used to profile the metabolomic changes induced in the T47d cells upon drug treatment. Results: Our results have demonstrated that celecoxib, a potent and selective COX-2 inhibitor, resulted in significant antiproliferative activity against all examined breast cancer cell lines with IC50 values of 95.44, 49.50. and 97.70 μM against MDA-MB-231, T47d, and MCF-7, respectively. Additionally, celecoxib exhibited a synergistic effect against T47d cells combined with raloxifene, a selective estrogen receptor modulator. Interestingly, celecoxib treatment increased cell apoptosis and resulted in substantial inhibition of cancer cell migration. In addition, the metabolomic analysis suggests that celecoxib may have affected metabolites (n = 43) that are involved in several pathways, including the tricarboxylic acid cycle, amino acids metabolism pathways, and energy production pathways in cancer cells. Conclusion: Celecoxib may possess potential therapeutic utility for breast cancer treatment as monotherapy or in combination therapy. The reported metabolic changes taking place upon celecoxib treatment may shed light on possible molecular targets mediating the antiproliferative activity of celecoxib in an independent manner of its COX-2 inhibition.

Colorectal cancer (CRC) is one of most common malignancies worldwide and its incidence is still growing. In spite of recent advances in targeted therapies, their clinical efficacy has been limited, non-curative and unaffordable. A growing body of literature indicates that CRC is a multi-modal disease, where a variety of factors within the tumor microenvironment play a significant role in its pathogenesis. For instance, imbalance in gut microbial profiles and impaired intestinal barrier function contribute to the overall intestinal inflammation and initiation of CRC. Moreover, persistent chronic inflammation favors a tumor microenvironment for the growth of cancer. In addition, autophagy or ‘self-eating’ is a surveillance mechanism involved in the degradation of cellular constituents that are generated under stressful conditions. Cancer stem cells (CSCs), on the other hand, engage in the onset of CRC and are able to endow cancer cells with chemo-resistance. Furthermore, the aberrant epigenetic alterations promote CRC. These evidences highlight the need for multi-targeted approaches that are not only safe and inexpensive but offer a more effective alternative to current generation of targeted drugs. Curcumin, derived from the plant Curcuma longa, represents one such option that has a long history of its use for a variety of chronic disease including cancer, in Indian ayurvedic and traditional Chinese medicine. Scientific evidence over the past few decades have overwhelmingly shown that curcumin exhibits a multitude of anti-cancer activities orchestrated through key signaling pathways associated with cancer. In this article, we will present a current update and perspective on this natural medicine – incorporating the basic cellular mechanisms it effects and the current state of clinical evidence, challenges and promise for its use as a cancer preventative and potential adjunct together with modern therapies for CRC patients.

Mushrooms, both edible and medicinal have received considerable attention against cancer due to their polysaccharides, polysaccharides-protein complexes and low molecular weight secondary metabolites content. Every year, millions of people die because of this disease. Existing cancer therapies are poised with questions of efficacy, toxicity and adverse effects, hence justifying the search for finding new, alternative and efficient means to fend off the disease. Mushrooms and their derived active molecules can prevent oncogenesis and tumour metastasis via directly inhibiting tumour cells growth or indirectly improving immunity functions and by acting as chemotherapy adjuvants. While the mechanisms of such effects are not fully known, the roles of the bioactive compounds on cell signaling pathways involved in the promotion and progression of the disease appear to be key, particularly in view of their role(s) in multiple cellular processes, including cell survival, proliferation, and differentiation. This review discusses the aberrant cell signaling pathways involved in inhibition of tumour cell growth as target for mushrooms and their bioactive compounds as well as the associated challenges for the molecules therein to be successfully considered as preventive/therapeutic agents against cancer.

Background Researchers take different positions when describing the effects of infrasound on the human body. Although several studies investigated the likely harmful effects of infrasound exposure from wind turbines a significant connection has not been found yet. There is evidence that infrasound interacts with cell metabolism and may disrupt cell membrane integrity. Objectives The suggested impairment of the cells’ ultrastructure by infrasound leads to the question of whether infrasound can be therapeutically used, for instance in cancer therapy. This review provides the current state of the literature. Method Current literature on infrasound in cancer therapy including all studies with the search terms ‘cancer’ and ‘infrasound’ were identified and reviewed until the year 2020. Results The present state of research reveals promising effects of targeted infrasound in cancer therapy. Infrasound directly affects the tumor cells’ ultrastructure and seems to sensitize several types of cancer to chemotherapy, presumably due to membrane permeabilization. The application of infrasound on tumor cells without other therapeutic agents demonstrates different effects that probably depend on the type of cells, the applied frequency and sound pressure level as well as the time of exposure. Conclusions The mechanism of infrasound on cancer cells is not completely understood yet, hence, further studies have to be conducted to clarify the ultrastructural and metabolic changes inside the tumor cells. The development of suitable infrasound generators for the application in a clinical setting would be an important course of action.