Caleb Smack, Benjamin Johnson, Julius O Nyalwidhe, O John Semmes, Lifang Yang
{"title":"Small extracellular vesicles: Roles and clinical application in prostate cancer.","authors":"Caleb Smack, Benjamin Johnson, Julius O Nyalwidhe, O John Semmes, Lifang Yang","doi":"10.1016/bs.acr.2024.05.008","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.05.008","url":null,"abstract":"<p><p>Prostate cancer is a significant health problem in the United States. It is remarkably heterogenous, ranging from slow growing disease amenable to active surveillance to highly aggressive forms requiring active treatments. Therefore, being able to precisely determine the nature of disease and appropriately match patients to available and/or novel therapeutics is crucial to improve patients' overall outcome and quality of life. Recently small extracellular vesicles (sEVs), a subset of nanoscale membranous vesicles secreted by various cells, have emerged as important analytes for liquid biopsy and promising vehicles for drug delivery. sEVs contain various biomolecules such as genetic material, proteins, and lipids that recapitulate the characteristics and state of their donor cells. The application of existing and newly developed technologies has resulted in an increased depth of knowledge about biophysical structures, biogenesis, and functions of sEVs. In prostate cancer patients, tumor-derived sEVs can be isolated from biofluids, commonly urine and blood. They mediate intercellular signaling within the tumor microenvironment and distal organ-specific sites, supporting cancer initiation, progression, and metastasis. A mounting body of evidence suggests that sEV components can be potent biomarkers for prostate cancer diagnosis, prognosis, and prediction of disease progression and treatment response. Due to enhanced circulation stability and bio-barrier permeability, sEVs can be also used as effective drug delivery carriers to improve the efficacy and specificity of anti-tumor therapies. This review discusses recent studies on sEVs in prostate cancer and is focused on their role as biomarkers and drug delivery vehicles in the clinical management of prostate cancer.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Therese Featherston, Martina Paumann-Page, Mark B Hampton
{"title":"Melanoma redox biology and the emergence of drug resistance.","authors":"Therese Featherston, Martina Paumann-Page, Mark B Hampton","doi":"10.1016/bs.acr.2024.06.004","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.06.004","url":null,"abstract":"<p><p>Melanoma is the deadliest form of skin cancer, with the loss of approximately 60,000 lives world-wide each year. Despite the development of targeted therapeutics, including compounds that have selectivity for mutant oncoproteins expressed only in cancer cells, many patients are either unresponsive to initial therapy or their tumors acquire resistance. This results in five-year survival rates of below 25%. New strategies that either kill drug-resistant melanoma cells or prevent their emergence would be extremely valuable. Melanoma, like other cancers, has long been described as being under increased oxidative stress, resulting in an increased reliance on antioxidant defense systems. Changes in redox homeostasis are most apparent during metastasis and during the metabolic reprogramming associated with the development of treatment resistance. This review discusses oxidative stress in melanoma, with a particular focus on targeting antioxidant pathways to limit the emergence of drug resistant cells.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asit K Paul, John W Melson, Samina Hirani, Selvaraj Muthusamy
{"title":"Systemic therapy landscape of advanced prostate cancer.","authors":"Asit K Paul, John W Melson, Samina Hirani, Selvaraj Muthusamy","doi":"10.1016/bs.acr.2024.04.004","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.04.004","url":null,"abstract":"<p><p>Prostate cancer is the most commonly diagnosed cancer in American men and 2nd leading cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is the backbone of treatment for advanced prostate cancer. Over the past several decades a number of new therapeutics, such as novel androgen receptor pathway inhibitors, targeted agents and radionuclide therapies, have been introduced for the treatment of prostate cancers. These agents have been demonstrated to improve clinical outcomes of prostate cancer patients in randomized clinical trials. In addition, new therapeutic strategies, such as early intensification of ADT, novel treatment combinations, and treatment sequencing, are expected to improve outcomes further. In this clinical review, we discuss the changing treatment landscape for advanced prostate cancer with a focus on new therapeutics.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the complexity: Advanced methods in analyzing DNA, RNA, and protein interactions.","authors":"Maria Leonor Peixoto, Esha Madan","doi":"10.1016/bs.acr.2024.06.010","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.06.010","url":null,"abstract":"<p><p>Exploring the intricate interplay within and between nucleic acids, as well as their interactions with proteins, holds pivotal significance in unraveling the molecular complexities steering cancer initiation and progression. To investigate these interactions, a diverse array of highly specific and sensitive molecular techniques has been developed. The selection of a particular technique depends on the specific nature of the interactions. Typically, researchers employ an amalgamation of these different techniques to obtain a comprehensive and holistic understanding of inter- and intramolecular interactions involving DNA-DNA, RNA-RNA, DNA-RNA, or protein-DNA/RNA. Examining nucleic acid conformation reveals alternative secondary structures beyond conventional ones that have implications for cancer pathways. Mutational hotspots in cancer often lie within sequences prone to adopting these alternative structures, highlighting the importance of investigating intra-genomic and intra-transcriptomic interactions, especially in the context of mutations, to deepen our understanding of oncology. Beyond these intramolecular interactions, the interplay between DNA and RNA leads to formations like DNA:RNA hybrids (known as R-loops) or even DNA:DNA:RNA triplex structures, both influencing biological processes that ultimately impact cancer. Protein-nucleic acid interactions are intrinsic cellular phenomena crucial in both normal and pathological conditions. In particular, genetic mutations or single amino acid variations can alter a protein's structure, function, and binding affinity, thus influencing cancer progression. It is thus, imperative to understand the differences between wild-type (WT) and mutated (MT) genes, transcripts, and proteins. The review aims to summarize the frequently employed methods and techniques for investigating interactions involving nucleic acids and proteins, highlighting recent advancements and diverse adaptations of each technique.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modular formation of in vitro tumor models for oncological research/therapeutic drug screening.","authors":"Weiwei Wang, Hongjun Wang","doi":"10.1016/bs.acr.2024.06.011","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.06.011","url":null,"abstract":"<p><p>In recognition of the lethal nature of cancer, extensive efforts have been made to understand the mechanistic causation while identifying the effective therapy modality in hope to eradicate cancerous cells with minimal damage to healthy cells. In search of such effective therapeutics, establishing pathophysiologically relevant in vitro models would be of importance in empowering our capabilities of truly identifying those potent ones with significantly reduction of the preclinical periods for rapid translation. In this regard, wealthy progresses have been achieved over past decades in establishing various in vitro and in vivo tumor models. Ideally, the tumor models should maximally recapture the key pathophysiological attributes of their native counterparts. Many of the current models have demonstrated their utilities but also showed some noticeable limitations. This book chapter will briefly review some of the mainstream platforms for in vitro tumor models followed by detailed elaboration on the modular strategies to form in vitro tumor models with complex structures and spatial organization of cellular components. Clearly, with the ability to modulate the building modules it becomes a new trend to form in vitro tumor models following a bottom-up approach, which offers a high flexibility to satisfy the needs for pathophysiological study, anticancer drug screening or design of personalized treatment.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jordan Hartig, Lyndsay E A Young, Grace Grimsley, Anand S Mehta, Joseph E Ippolito, Robin J Leach, Peggi M Angel, Richard R Drake
{"title":"The glycosylation landscape of prostate cancer tissues and biofluids.","authors":"Jordan Hartig, Lyndsay E A Young, Grace Grimsley, Anand S Mehta, Joseph E Ippolito, Robin J Leach, Peggi M Angel, Richard R Drake","doi":"10.1016/bs.acr.2024.04.005","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.04.005","url":null,"abstract":"<p><p>An overview of the role of glycosylation in prostate cancer (PCa) development and progression is presented, focusing on recent advancements in defining the N-glycome through glycomic profiling and glycoproteomic methodologies. Glycosylation is a common post-translational modification typified by oligosaccharides attached N-linked to asparagine or O-linked to serine or threonine on carrier proteins. These attached sugars have crucial roles in protein folding and cellular recognition processes, such that altered glycosylation is a hallmark of cancer pathogenesis and progression. In the past decade, advancements in N-glycan profiling workflows using Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) technology have been applied to define the spatial distribution of glycans in PCa tissues. Multiple studies applying N-glycan MALDI-MSI to pathology-defined PCa tissues have identified significant alterations in N-glycan profiles associated with PCa progression. N-glycan compositions progressively increase in number, and structural complexity due to increased fucosylation and sialylation. Additionally, significant progress has been made in defining the glycan and glycopeptide compositions of prostatic-derived glycoproteins like prostate-specific antigen in tissues and biofluids. The glycosyltransferases involved in these changes are potential drug targets for PCa, and new approaches in this area are summarized. These advancements will be discussed in the context of the further development of clinical diagnostics and therapeutics targeting glycans and glycoproteins associated with PCa progression. Integration of large scale spatial glycomic data for PCa with other spatial-omic methodologies is now feasible at the tissue and single-cell levels.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Zhang, Zhi-Wei Ye, Danyelle M Townsend, Kenneth D Tew
{"title":"Redox pathways in melanoma.","authors":"Jie Zhang, Zhi-Wei Ye, Danyelle M Townsend, Kenneth D Tew","doi":"10.1016/bs.acr.2024.06.002","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.06.002","url":null,"abstract":"<p><p>Cases of melanoma are doubling every 12 years, and in stages III and IV, the disease is associated with high mortality rates concomitant with unresectable metastases and therapeutic drug resistance. Despite some advances in treatment success, there is a marked need to understand more about the pathology of the disease. The present review provides an overview of how melanoma cells use and modulate redox pathways to facilitate thiol homeostasis and melanin biosynthesis and describes plausible redox targets that may improve therapeutic approaches in managing malignant disease and metastasis. Melanotic melanoma has some unique characteristics. Making melanin requires a considerable dedication of cellular energy resources and utilizes glutathione and glutathione transferases in certain steps in the biosynthetic pathway. Melanin is an antioxidant but is also functionally important in hematopoiesis and influential in various aspects of host immune responses, giving it unique characteristics. Together with other redox traits that are specific to melanoma, a discussion of possible therapeutic approaches is also provided.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amit Kumar, Luni Emdad, Swadesh K Das, Paul B Fisher
{"title":"Recent advances and progress in immunotherapy of solid cancers.","authors":"Amit Kumar, Luni Emdad, Swadesh K Das, Paul B Fisher","doi":"10.1016/bs.acr.2024.05.004","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.05.004","url":null,"abstract":"<p><p>Adoptive cell therapy using chimeric antigen receptor (CAR) technology has become mainstream by employing advanced engineering platforms to promote cancer immunotherapy. CAR T cells have shown remarkable efficacy in the treatment of hematological malignancies; however, the value of this therapy remains inconclusive in the context of solid tumors. Immunotherapy of solid tumors is restrained by several obstacles including the presence of an immunosuppressive tumor microenvironment (TME), limited tumor trafficking, inhibited immune cell infiltration, absence of tumor-specific antigens, and off-target toxicity and adverse events associated with these therapies. Despite recent advances in CAR T cell construction, including the integration of co-stimulatory domains and the creation of armed CAR T cells, with promising outcomes in the treatment of some solid tumors, there are still many unresolved obstacles that need to be overcome. To surmount these impediments to effective CAR T cell therapies, other immune cells, such as natural killer cells and macrophages, have been engineered to serve as appealing alternatives for successful cancer immunotherapy of solid tumors. CAR NK cells demonstrate significant clinical advantages due to their ready availability and minimal toxicity. CAR macrophage (M) cells provide considerable therapeutic potential due to their ability to penetrate the TME of solid tumors. In this review, we comprehensively examine the latest developments and prospects of engineered immune cell-based cancer immunotherapies specifically designed for treating solid tumors. In addition, we provide a concise overview of current clinical trials that are examining the safety and effectiveness of modified immune cells, such as CAR T, CAR NK, and CAR M, in their ability to specifically target solid tumors and promote improved therapeutic outcomes in patients with diverse solid cancers.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linbu Liao, Patrick C N Martin, Hyobin Kim, Sanaz Panahandeh, Kyoung Jae Won
{"title":"Data enhancement in the age of spatial biology.","authors":"Linbu Liao, Patrick C N Martin, Hyobin Kim, Sanaz Panahandeh, Kyoung Jae Won","doi":"10.1016/bs.acr.2024.06.008","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.06.008","url":null,"abstract":"<p><p>Unveiling the intricate interplay of cells in their native environment lies at the heart of understanding fundamental biological processes and unraveling disease mechanisms, particularly in complex diseases like cancer. Spatial transcriptomics (ST) offers a revolutionary lens into the spatial organization of gene expression within tissues, empowering researchers to study both cell heterogeneity and microenvironments in health and disease. However, current ST technologies often face limitations in either resolution or the number of genes profiled simultaneously. Integrating ST data with complementary sources, such as single-cell transcriptomics and detailed tissue staining images, presents a powerful solution to overcome these limitations. This review delves into the computational approaches driving the integration of spatial transcriptomics with other data types. By illuminating the key challenges and outlining the current algorithmic solutions, we aim to highlight the immense potential of these methods to revolutionize our understanding of cancer biology.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathleen C Brown, Amanda M Sugrue, Kaitlyn B Conley, Kushal J Modi, Reagan S Light, Ashley J Cox, Christopher R Bender, Sarah L Miles, Krista L Denning, Paul T Finch, Joshua A Hess, Maria T Tirona, Monica A Valentovic, Piyali Dasgupta
{"title":"Anti-cancer activity of capsaicin and its analogs in gynecological cancers.","authors":"Kathleen C Brown, Amanda M Sugrue, Kaitlyn B Conley, Kushal J Modi, Reagan S Light, Ashley J Cox, Christopher R Bender, Sarah L Miles, Krista L Denning, Paul T Finch, Joshua A Hess, Maria T Tirona, Monica A Valentovic, Piyali Dasgupta","doi":"10.1016/bs.acr.2024.05.005","DOIUrl":"10.1016/bs.acr.2024.05.005","url":null,"abstract":"<p><p>Capsaicin is the hot and pungent ingredient of chili peppers. It is a potent pain-relieving agent and is often present in over-the-counter analgesic lotions and creams. Several convergent studies reveal that capsaicin displays growth-suppressive activity in human cancers in vitro and in vivo. Apart from its growth-suppressive activity (as a single agent), capsaicin has been found to sensitize human cancer cells to the pro-apoptotic effects of chemotherapy and radiation. The first part of this book chapter discusses the anti-cancer activity of capsaicin in gynecological cancers in cell culture experiments and mouse models. Out of all gynecological cancers, the anti-cancer activity of capsaicin (and its analogs) has only been investigated in cervical cancers and ovarian cancers. The clinical development of capsaicin as a viable anti-cancer drug has remained challenging due to its poor bioavailability and aqueous solubility properties. In addition, the administration of capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, irritation in the gut, nausea diarrhea and vomiting. Two strategies have been investigated to overcome these drawbacks of capsaicin. The first is to encapsulate capsaicin in sustained release drug delivery systems. The second strategy is to design non-pungent capsaicin analogs which will retain the anti-tumor activity of capsaicin. The second part of this chapter provides an overview of the anti-neoplastic (and chemosensitization activity) of capsaicin analogs and capsaicin-based sustained release formulations in cervical and ovarian cancers. The design of selective non-pungent capsaicin analogs and capsaicin-based polymeric drug delivery systems may foster the hope of novel strategies for the treatment and management of gynecological cancers.</p>","PeriodicalId":94294,"journal":{"name":"Advances in cancer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}