Deep learning-based identification of esophageal cancer subtypes through analysis of high-resolution histopathology images.

Esophageal cancer (EC) remains a significant health challenge globally, with increasing incidence and high mortality rates. Despite advances in treatment, there remains a need for improved diagnostic methods and understanding of disease progression. This study addresses the significant challenges in the automatic classification of EC, particularly in distinguishing its primary subtypes: adenocarcinoma and squamous cell carcinoma, using histopathology images. Traditional histopathological diagnosis, while being the gold standard, is subject to subjectivity and human error and imposes a substantial burden on pathologists. This study proposes a binary class classification system for detecting EC subtypes in response to these challenges. The system leverages deep learning techniques and tissue-level labels for enhanced accuracy. We utilized 59 high-resolution histopathological images from The Cancer Genome Atlas (TCGA) Esophageal Carcinoma dataset (TCGA-ESCA). These images were preprocessed, segmented into patches, and analyzed using a pre-trained ResNet101 model for feature extraction. For classification, we employed five machine learning classifiers: Support Vector Classifier (SVC), Logistic Regression (LR), Decision Tree (DT), AdaBoost (AD), Random Forest (RF), and a Feed-Forward Neural Network (FFNN). The classifiers were evaluated based on their prediction accuracy on the test dataset, yielding results of 0.88 (SVC and LR), 0.64 (DT and AD), 0.82 (RF), and 0.94 (FFNN). Notably, the FFNN classifier achieved the highest Area Under the Curve (AUC) score of 0.92, indicating its superior performance, followed closely by SVC and LR, with a score of 0.87. This suggested approach holds promising potential as a decision-support tool for pathologists, particularly in regions with limited resources and expertise. The timely and precise detection of EC subtypes through this system can substantially enhance the likelihood of successful treatment, ultimately leading to reduced mortality rates in patients with this aggressive cancer.

Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes.

Extracellular vesicles as tools and targets in therapy for diseases.

Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery.

CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond.

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties.

The potential modulation of gut microbiota and oxidative stress by dietary carotenoid pigments.

Gut microbiota plays a crucial role in regulating the response to immune checkpoint therapy, therefore modulation of the microbiome with bioactive molecules like carotenoids might be a very effective strategy to reduce the risk of chronic diseases. This review highlights the bio-functional effect of carotenoids on Gut Microbiota modulation based on a bibliographic search of the different databases. The methodology given in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) has been employed for developing this review using papers published over two decades considering keywords related to carotenoids and gut microbiota. Moreover, studies related to the health-promoting properties of carotenoids and their utilization in the modulation of gut microbiota have been presented. Results showed that there can be quantitative changes in intestinal bacteria as a function of the type of carotenoid. Due to the dependency on several factors, gut microbiota continues to be a broad and complex study subject. Carotenoids are promising in the modulation of Gut Microbiota, which favored the appearance of beneficial bacteria, resulting in the protection of villi and intestinal permeability. In conclusion, it can be stated that carotenoids may help to protect the integrity of the intestinal epithelium from pathogens and activate immune cells.

Gut microbiota plays an essential role in regulating the immune checkpoint therapyCarotenoids are promising molecules in the alteration of gut microbiotaCarotenoids activate the immune cells resulting in a low incidence of oxidative stress.

Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India.

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings.

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor antigen escape, but their efficacy could be limited in cases where certain tumor cells do not express the targeted antigens. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors, including lack of reliable tumor-associated antigens, hypoxic cores, immunosuppressive tumor environments, enhanced reactive oxygen species, and decreased T-cell infiltration. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells. This review covers the evolution of CAR-T therapy against various tumors, including hematological and solid tumors, highlights challenges faced by CAR-T cell therapy, and suggests strategies to overcome these obstacles, such as utilizing single-cell RNA sequencing and artificial intelligence to optimize clinical-grade CAR-T cells.

Long non-coding RNAs modulate tumor microenvironment to promote metastasis: novel avenue for therapeutic intervention.

Cancer is a devastating disease and the primary cause of morbidity and mortality worldwide, with cancer metastasis responsible for 90% of cancer-related deaths. Cancer metastasis is a multistep process characterized by spreading of cancer cells from the primary tumor and acquiring molecular and phenotypic changes that enable them to expand and colonize in distant organs. Despite recent advancements, the underlying molecular mechanism(s) of cancer metastasis is limited and requires further exploration. In addition to genetic alterations, epigenetic changes have been demonstrated to play an important role in the development of cancer metastasis. Long non-coding RNAs (lncRNAs) are considered one of the most critical epigenetic regulators. By regulating signaling pathways and acting as decoys, guides, and scaffolds, they modulate key molecules in every step of cancer metastasis such as dissemination of carcinoma cells, intravascular transit, and metastatic colonization. Gaining a good knowledge of the detailed molecular basis underlying lncRNAs regulating cancer metastasis may provide previously unknown therapeutic and diagnostic lncRNAs for patients with metastatic disease. In this review, we concentrate on the molecular mechanisms underlying lncRNAs in the regulation of cancer metastasis, the cross-talk with metabolic reprogramming, modulating cancer cell anoikis resistance, influencing metastatic microenvironment, and the interaction with pre-metastatic niche formation. In addition, we also discuss the clinical utility and therapeutic potential of lncRNAs for cancer treatment. Finally, we also represent areas for future research in this rapidly developing field.

Cyclin-dependent kinases in cancer: Role, regulation, and therapeutic targeting.

Regulated cell division is one of the fundamental phenomena which is the basis of all life on earth. Even a single base pair mutation in DNA leads to the production of the dysregulated protein that can have catastrophic consequences. Cell division is tightly controlled and orchestrated by proteins called cyclins and cyclin-dependent kinase (CDKs), which serve as licensing factors during different phases of cell division. Dysregulated cell division is one of the most important hallmarks of cancer and is commonly associated with a mutation in cyclins and CDKs along with tumor suppressor proteins. Therefore, targeting the component of the cell cycle which leads to these characteristics would be an effective strategy for treating cancers. Specifically, Cyclin-dependent kinases (CDKs) involved in cell cycle regulation have been identified to be overexpressed in many cancers. Many studies indicate that oncogenesis occurs in cancerous cells by the overactivity of different CDKs, which impact cell cycle progression and checkpoint dysregulation which is responsible for development of tumor. The development of CDK inhibitors has emerged as a promising and novel approach for cancer treatment in both solid and hematological malignancies. Some of the novel CDK inhibitors have shown remarkable results in clinical trials, such as-Ribociclib®, Palbociclib® and Abemaciclib®, which are CDK4/6 inhibitors and have received FDA approval for the treatment of breast cancer. In this chapter, we discuss the molecular mechanism through which cyclins and CDKs regulate cell cycle progression and the emergence of cyclins and CDKs as rational targets in cancer. We also discuss recent advances in developing CDK inhibitors, which have emerged as a novel class of inhibitors, and their associated toxicities in recent years.

Ubiquitin specific peptidase 37 and PCNA interaction promotes osteosarcoma pathogenesis by modulating replication fork progression.

BACKGROUND: Osteosarcoma is a type of bone cancer that predominantly affects young individuals, including children and adolescents. The disease progresses through heterogeneous genetic alterations, and patients often develop pulmonary metastases even after the primary tumors have been surgically removed. Ubiquitin-specific peptidases (USPs) regulate several critical cellular processes, such as cell cycle progression, transcriptional activation, and signal transduction. Various studies have revealed the significance of USP37 in the regulation of replication stress and oncogenesis. METHODS: In this study, the Cancer Genome Atlas (TCGA) database was analyzed to investigate USP37 expression. RNA sequencing was utilized to assess the impact of USP37 overexpression and depletion on gene expression in osteosarcoma cells. Various molecular assays, including colony formation, immunofluorescence, immunoprecipitation, and DNA replication restart, were employed to examine the physical interaction between USP37 and PCNA, as well as its physiological effects in osteosarcoma cells. Additionally, molecular docking studies were conducted to gain insight into the nature of the interaction between USP37 and PCNA. Furthermore, immunohistochemistry was performed on archived tissue blocks from osteosarcoma patients to establish a correlation between USP37 and PCNA expression. RESULTS: Analysis of the TCGA database revealed that increased expression of USP37 was linked to decreased progression-free survival (PFS) in osteosarcoma patients. Next-generation sequencing analysis of osteosarcoma cells demonstrated that overexpression or knockdown of USP37 led to the expression of different sets of genes. USP37 overexpression provided a survival advantage, while its depletion heightened sensitivity to replication stress in osteosarcoma cells. USP37 was found to physically interact with PCNA, and molecular docking studies indicated that the interaction occurs through unique residues. In response to genotoxic stress, cells that overexpressed USP37 resolved DNA damage foci more quickly than control cells or cells in which USP37 was depleted. The expression of USP37 varied in archived osteosarcoma tissues, with intermediate expression seen in 52% of cases in the cohort examined. CONCLUSION: The results of this investigation propose that USP37 plays a vital role in promoting replication stress tolerance in osteosarcoma cells. The interaction between USP37 and PCNA is involved in the regulation of replication stress, and disrupting it could potentially trigger synthetic lethality in osteosarcoma. This study has expanded our knowledge of the mechanism through which USP37 regulates replication stress, and its potential as a therapeutic target in osteosarcoma merits additional exploration.

Current and emerging biomarkers in ovarian cancer diagnosis; CA125 and beyond.

Ovarian cancer (OC) is one of the most common causes of cancer-related death in women worldwide. Its five-year survival rates are worse than the two most common gynecological cancers, cervical and endometrial. This is because it is asymptomatic in the early stages and usually detected in the advanced metastasized stage. Thus, survival is increasingly dependent on timely diagnosis. The delay in detection is contributed partly by the occurrence of non-specific clinical symptoms in the early stages and the lack of effective biomarkers and detection approaches. This underlines the need for biomarker identification and clinical validation, enabling earlier diagnosis, effective prognosis, and response to therapy. Apart from the traditional diagnostic biomarkers for OC, several new biomarkers have been delineated using advanced high-throughput molecular approaches in recent years. They are currently being clinically evaluated for their true diagnostic potential. In this chapter, we document the commonly utilized traditional screening markers and recently identified emerging biomarkers in OC diagnosis, focusing on secretory and protein biomarkers. We also briefly reviewed the recent advances and prospects in OC diagnosis.

Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics.

Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system's pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.

Natural products as chemo-radiation therapy sensitizers in cancers.

Cancer is a devastating disease and is the second leading cause of death worldwide. Surgery, chemotherapy (CT), and/or radiation therapy (RT) are the treatment of choice for most advanced tumors. Unfortunately, treatment failure due to intrinsic and acquired resistance to the current CT and RT is a significant challenge associated with poor patient prognosis. There is an urgent need to develop and identify agents that can sensitize tumor cells to chemo-radiation therapy (CRT) with minimal cytotoxicity to the healthy tissues. While many recent studies have identified the underlying molecular mechanisms and therapeutic targets for CRT failure, using small molecule inhibitors to chemo/radio sensitize tumors is associated with high toxicity and increased morbidity. Natural products have long been used as chemopreventive agents in many cancers. Combining many of these compounds with the standard chemotherapeutic agents or with RT has shown synergistic effects on cancer cell death and overall improvement in patient survival. Based on the available data, there is strong evidence that natural products have a robust therapeutic potential along with CRT and their well-known chemopreventive effects in many solid tumors. This review article reports updated literature on different natural products used as CT or RT sensitizers in many solid tumors. This is the first review discussing CT and RT sensitizers together in cancer.

Cytokine- and chemokine-induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy.

Colorectal cancer (CRC) is a predominant life-threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer-associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell-like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine- and chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine- and chemokine-mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

Chemokines in triple-negative breast cancer heterogeneity: New challenges for clinical implications.

Tumor heterogeneity is a hallmark of cancer and one of the primary causes of resistance to therapies. Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers and is the most aggressive subtype, is very diverse, connected to metastatic potential and response to therapy. It is a very diverse disease at the molecular, pathologic, and clinical levels. TNBC is substantially more likely to recur and has a worse overall survival rate following diagnosis than other breast cancer subtypes. Chemokines, low molecular weight proteins that stimulate chemotaxis, have been shown to control the cues responsible for TNBC heterogeneity. In this review, we have focused on tumor heterogeneity and the role of chemokines in modulating tumor heterogeneity, since this is the most critical issue in treating TNBC. Additionally, we examined numerous cues mediated by chemokine networks that contribute to the heterogeneity of TNBC. Recent developments in our knowledge of the chemokine networks that regulate TNBC heterogeneity may pave the way for developing effective therapeutic modalities for effective treatment of TNBC.

Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments.

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.

miRNAs as novel immunoregulators in cancer.

The immune system is a well-known vital regulator of tumor growth, and one of the main hallmarks of cancer is evading the immune system. Immune system deregulation can lead to immune surveillance evasion, sustained cancer growth, proliferation, and metastasis. Tumor-mediated disruption of the immune system is accomplished by different mechanisms that involve extensive crosstalk with the immediate microenvironment, which includes endothelial cells, immune cells, and stromal cells, to create a favorable tumor niche that facilitates the development of cancer. The essential role of non-coding RNAs such as microRNAs (miRNAs) in the mechanism of cancer cell immune evasion has been highlighted in recent studies. miRNAs are small non-coding RNAs that regulate a wide range of post-transcriptional gene expression in a cell. Recent studies have focused on the function that miRNAs play in controlling the expression of target proteins linked to immune modulation. Studies show that miRNAs modulate the immune response in cancers by regulating the expression of different immune-modulatory molecules associated with immune effector cells, such as macrophages, dendritic cells, B-cells, and natural killer cells, as well as those present in tumor cells and the tumor microenvironment. This review explores the relationship between miRNAs, their altered patterns of expression in tumors, immune modulation, and the functional control of a wide range of immune cells, thereby offering detailed insights on the crosstalk of tumor-immune cells and their use as prognostic markers or therapeutic agents.

Ubiquitin-specific peptidase 37: an important cog in the oncogenic machinery of cancerous cells.

Protein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics.