Pub Date : 2024-01-01Epub Date: 2024-05-03DOI: 10.1016/bs.acr.2024.04.001
Elias S J Arnér, Edward E Schmidt
Cysteine is required for synthesis of glutathione (GSH), coenzyme A, other sulfur-containing metabolites, and most proteins. In most cells, cysteine comes from extracellular disulfide sources including cystine, glutathione-disulfide, and peptides. The thioredoxin reductase-1 (TrxR1)- or glutathione-disulfide reductase (GSR)-driven enzymatic systems can fuel cystine reduction via thioredoxins, glutaredoxins, or other thioredoxin-fold proteins. Free cystine enters cells thorough the cystine-glutamate antiporter, xCT, but systemically, plasma glutathione-disulfide might predominate as a cystine source. Erastin, inhibiting both xCT and voltage-dependent anion channels, induces ferroptotic cell death, so named because this type of cell death is antagonized by iron-chelators. Many cancer cells seem to be predisposed to ferroptosis, which has been proposed as a targetable cancer liability. Ferroptosis is associated with lipid peroxidation and loss of either glutathione peroxidase-4 (GPX4) or ferroptosis suppressor protein-1 (FSP1), which each prevent accumulation of lipid peroxides. It has been suggested that an xCT inhibition-induced cellular cysteine-deficiency lowers GSH levels, starving GPX4 for reducing power and allowing membrane lipid peroxides to accumulate, thereby causing ferroptosis. Aspects of ferroptosis are however not fully understood and need to be further scrutinized, for example that neither disruption of GSH synthesis, loss of GSH, nor disruption of glutathione disulfide reductase (GSR), triggers ferroptosis in animal models. Here we reevaluate the relationships between Erastin, xCT, GPX4, cellular cysteine and GSH, RSL3 or ML162, and ferroptosis. We conclude that, whereas both Cys and ferroptosis are potential liabilities in cancer, their relationship to each other remains insufficiently understood.
{"title":"Unresolved questions regarding cellular cysteine sources and their possible relationships to ferroptosis.","authors":"Elias S J Arnér, Edward E Schmidt","doi":"10.1016/bs.acr.2024.04.001","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.04.001","url":null,"abstract":"<p><p>Cysteine is required for synthesis of glutathione (GSH), coenzyme A, other sulfur-containing metabolites, and most proteins. In most cells, cysteine comes from extracellular disulfide sources including cystine, glutathione-disulfide, and peptides. The thioredoxin reductase-1 (TrxR1)- or glutathione-disulfide reductase (GSR)-driven enzymatic systems can fuel cystine reduction via thioredoxins, glutaredoxins, or other thioredoxin-fold proteins. Free cystine enters cells thorough the cystine-glutamate antiporter, xCT, but systemically, plasma glutathione-disulfide might predominate as a cystine source. Erastin, inhibiting both xCT and voltage-dependent anion channels, induces ferroptotic cell death, so named because this type of cell death is antagonized by iron-chelators. Many cancer cells seem to be predisposed to ferroptosis, which has been proposed as a targetable cancer liability. Ferroptosis is associated with lipid peroxidation and loss of either glutathione peroxidase-4 (GPX4) or ferroptosis suppressor protein-1 (FSP1), which each prevent accumulation of lipid peroxides. It has been suggested that an xCT inhibition-induced cellular cysteine-deficiency lowers GSH levels, starving GPX4 for reducing power and allowing membrane lipid peroxides to accumulate, thereby causing ferroptosis. Aspects of ferroptosis are however not fully understood and need to be further scrutinized, for example that neither disruption of GSH synthesis, loss of GSH, nor disruption of glutathione disulfide reductase (GSR), triggers ferroptosis in animal models. Here we reevaluate the relationships between Erastin, xCT, GPX4, cellular cysteine and GSH, RSL3 or ML162, and ferroptosis. We conclude that, whereas both Cys and ferroptosis are potential liabilities in cancer, their relationship to each other remains insufficiently understood.</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":"141790741","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}
Pub Date : 2024-01-01Epub Date: 2024-06-22DOI: 10.1016/bs.acr.2024.06.001
Sheeraz Un Nazir, Juhi Mishra, Shailendra Kumar Maurya, Negin Ziamiavaghi, Sanika Bodas, Benjamin A Teply, Samikshan Dutta, Kaustubh Datta
Prostate cancer, one of the most frequently diagnosed cancers in men, leads to significant mortality worldwide. Its study is important due to the complexity and diversity in its progression, highlighting the urgent need for improved therapeutic strategies. This chapter probes into the genetic and epigenetic factors influencing prostate cancer progression, underscoring the importance of understanding the disease's molecular fundamentals for the development of targeted therapies. It specifically reviews the role of key genetic mutations in genes such as Androgen Receptor, TP53, SPOP, FOXA1 and PTEN which are crucial for the disease onset and a progression. Furthermore, it examines the impact of epigenetic modifications, including DNA methylation and histone modification, which contribute to the cancer's progression by affecting gene expression and cellular behavior. Further, in this chapter we delve into the underlying signaling mechanism, the advancements in targeting genetic and epigenetic alterations in prostate cancer. These findings have revealed promising targets for therapeutic advancements, aiming to understand and identify promising avenues for future therapies. This chapter improves our current understanding of prostate cancer genetic and epigenetic landscape, emphasizing the necessity of advancing our knowledge to refine and expand treatment options for prostate cancer patients.
前列腺癌是最常见的男性癌症之一,在全球范围内导致大量死亡。由于前列腺癌进展的复杂性和多样性,对前列腺癌的研究显得尤为重要,这也凸显了改进治疗策略的迫切需要。本章探讨了影响前列腺癌进展的遗传和表观遗传因素,强调了了解该疾病的分子基础对开发靶向疗法的重要性。它特别回顾了雄激素受体、TP53、SPOP、FOXA1 和 PTEN 等基因中关键遗传突变的作用,这些基因对疾病的发生和发展至关重要。此外,本章还探讨了表观遗传修饰(包括 DNA 甲基化和组蛋白修饰)的影响,这些修饰通过影响基因表达和细胞行为促进癌症进展。此外,本章还深入探讨了前列腺癌的基本信号转导机制、针对基因和表观遗传学改变的研究进展。这些发现揭示了有前景的治疗目标,旨在了解和确定未来治疗的可行途径。本章加深了我们目前对前列腺癌基因和表观遗传学状况的了解,强调了我们有必要增进知识,以完善和扩大前列腺癌患者的治疗方案。
{"title":"Deciphering the genetic and epigenetic architecture of prostate cancer.","authors":"Sheeraz Un Nazir, Juhi Mishra, Shailendra Kumar Maurya, Negin Ziamiavaghi, Sanika Bodas, Benjamin A Teply, Samikshan Dutta, Kaustubh Datta","doi":"10.1016/bs.acr.2024.06.001","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.06.001","url":null,"abstract":"<p><p>Prostate cancer, one of the most frequently diagnosed cancers in men, leads to significant mortality worldwide. Its study is important due to the complexity and diversity in its progression, highlighting the urgent need for improved therapeutic strategies. This chapter probes into the genetic and epigenetic factors influencing prostate cancer progression, underscoring the importance of understanding the disease's molecular fundamentals for the development of targeted therapies. It specifically reviews the role of key genetic mutations in genes such as Androgen Receptor, TP53, SPOP, FOXA1 and PTEN which are crucial for the disease onset and a progression. Furthermore, it examines the impact of epigenetic modifications, including DNA methylation and histone modification, which contribute to the cancer's progression by affecting gene expression and cellular behavior. Further, in this chapter we delve into the underlying signaling mechanism, the advancements in targeting genetic and epigenetic alterations in prostate cancer. These findings have revealed promising targets for therapeutic advancements, aiming to understand and identify promising avenues for future therapies. This chapter improves our current understanding of prostate cancer genetic and epigenetic landscape, emphasizing the necessity of advancing our knowledge to refine and expand treatment options for prostate cancer patients.</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":"141736277","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}
Worldwide, prostate cancer (PCa) remains a leading cause of death in men. Histologically, the majority of PCa cases are classified as adenocarcinomas, which are mainly composed of androgen receptor-positive luminal cells. PCa is initially driven by the androgen receptor axis, where androgen-mediated activation of the receptor is one of the primary culprits for disease progression. Therefore, in advanced stage PCa, patients are generally treated with androgen deprivation therapies alone or in combination with androgen receptor pathway inhibitors. However, after an initial decrease, the cancer recurs for majority patients. At this stage, cancer is known as castration-resistant prostate cancer (CRPC). Majority of CRPC tumors still depend on androgen receptor axis for its progression to metastasis. However, in around 20-30% of cases, CRPC progresses via an androgen receptor-independent pathway and is often presented as neuroendocrine cancer (NE). This NE phenotype is highly aggressive with poor overall survival as compared to CRPC adenocarcinoma. NE cancers are resistant to standard taxane chemotherapies, which are often used to treat metastatic disease. Pathologically and morphologically, NE cancers are highly diverse and often co-exist with adenocarcinoma. Due to the lack of proper biomarkers, it is often difficult to make an early diagnosis of this lethal disease. Moreover, increased tumor heterogeneity and admixtures of adeno and NE subtypes in the same tumor make early detection of NE tumors very difficult. With the advancement of our knowledge and sequencing technology, we are now able to better understand the molecular mediators of this transformation pathway. This current study will give an update on how various molecular regulators are involved in these lineage transformation processes and what challenges we are still facing to detect and treat this cancer.
在全球范围内,前列腺癌(PCa)仍然是导致男性死亡的主要原因。从组织学角度看,大多数 PCa 病例属于腺癌,主要由雄激素受体阳性的管腔细胞组成。PCa 最初由雄激素受体轴驱动,雄激素介导的受体激活是疾病进展的罪魁祸首之一。因此,对于晚期 PCa 患者,一般采用雄激素剥夺疗法单独治疗或与雄激素受体通路抑制剂联合治疗。然而,大多数患者的病情在初步缓解后又会复发。在这一阶段,癌症被称为阉割抵抗性前列腺癌(CRPC)。大多数 CRPC 肿瘤仍依赖雄激素受体轴进行转移。不过,约有 20%-30% 的 CRPC 会通过雄激素受体依赖性途径发展,通常表现为神经内分泌癌(NE)。与 CRPC 腺癌相比,这种 NE 表型具有高度侵袭性,总生存率较低。NE 癌症对标准的类固醇化疗具有抗药性,而类固醇化疗通常用于治疗转移性疾病。从病理和形态上看,NE 癌具有高度多样性,并经常与腺癌并存。由于缺乏适当的生物标志物,通常很难对这种致命疾病做出早期诊断。此外,肿瘤异质性的增加以及同一肿瘤中腺癌和 NE 亚型的混合,也使 NE 肿瘤的早期检测变得非常困难。随着知识和测序技术的进步,我们现在能够更好地了解这一转化途径的分子介质。本研究将介绍各种分子调控因子是如何参与这些细胞系转化过程的,以及我们在检测和治疗这种癌症方面仍面临哪些挑战。
{"title":"Understanding the molecular regulators of neuroendocrine prostate cancer.","authors":"Sreyashi Bhattacharya, Avery Stillahn, Kaitlin Smith, Michael Muders, Kaustubh Datta, Samikshan Dutta","doi":"10.1016/bs.acr.2024.04.006","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.04.006","url":null,"abstract":"<p><p>Worldwide, prostate cancer (PCa) remains a leading cause of death in men. Histologically, the majority of PCa cases are classified as adenocarcinomas, which are mainly composed of androgen receptor-positive luminal cells. PCa is initially driven by the androgen receptor axis, where androgen-mediated activation of the receptor is one of the primary culprits for disease progression. Therefore, in advanced stage PCa, patients are generally treated with androgen deprivation therapies alone or in combination with androgen receptor pathway inhibitors. However, after an initial decrease, the cancer recurs for majority patients. At this stage, cancer is known as castration-resistant prostate cancer (CRPC). Majority of CRPC tumors still depend on androgen receptor axis for its progression to metastasis. However, in around 20-30% of cases, CRPC progresses via an androgen receptor-independent pathway and is often presented as neuroendocrine cancer (NE). This NE phenotype is highly aggressive with poor overall survival as compared to CRPC adenocarcinoma. NE cancers are resistant to standard taxane chemotherapies, which are often used to treat metastatic disease. Pathologically and morphologically, NE cancers are highly diverse and often co-exist with adenocarcinoma. Due to the lack of proper biomarkers, it is often difficult to make an early diagnosis of this lethal disease. Moreover, increased tumor heterogeneity and admixtures of adeno and NE subtypes in the same tumor make early detection of NE tumors very difficult. With the advancement of our knowledge and sequencing technology, we are now able to better understand the molecular mediators of this transformation pathway. This current study will give an update on how various molecular regulators are involved in these lineage transformation processes and what challenges we are still facing to detect and treat this 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":"141736301","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}
Pub Date : 2024-01-01Epub Date: 2024-04-25DOI: 10.1016/bs.acr.2024.04.003
Yuqian Gao, Hyeyoon Kim, Reta Birhanu Kitata, Tai-Tu Lin, Adam C Swensen, Tujin Shi, Tao Liu
Prostate cancer (PCa) is the most common non-skin cancer among men in the United States. However, the widely used protein biomarker in PCa, prostate-specific antigen (PSA), while useful for initial detection, its use alone cannot detect aggressive PCa and can lead to overtreatment. This chapter provides an overview of PCa protein biomarker development. It reviews the state-of-the-art liquid chromatography-mass spectrometry-based proteomics technologies for PCa biomarker development, such as enhancing the detection sensitivity of low-abundance proteins through antibody-based or antibody-independent protein/peptide enrichment, enriching post-translational modifications such as glycosylation as well as information-rich extracellular vesicles, and increasing accuracy and throughput using advanced data acquisition methodologies. This chapter also summarizes recent PCa biomarker validation studies that applied those techniques in diverse specimen types, including cell lines, tissues, proximal fluids, urine, and blood, developing novel protein biomarkers for various clinical applications, including early detection and diagnosis, prognosis, and therapeutic intervention of PCa.
{"title":"Multiplexed quantitative proteomics in prostate cancer biomarker development.","authors":"Yuqian Gao, Hyeyoon Kim, Reta Birhanu Kitata, Tai-Tu Lin, Adam C Swensen, Tujin Shi, Tao Liu","doi":"10.1016/bs.acr.2024.04.003","DOIUrl":"10.1016/bs.acr.2024.04.003","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most common non-skin cancer among men in the United States. However, the widely used protein biomarker in PCa, prostate-specific antigen (PSA), while useful for initial detection, its use alone cannot detect aggressive PCa and can lead to overtreatment. This chapter provides an overview of PCa protein biomarker development. It reviews the state-of-the-art liquid chromatography-mass spectrometry-based proteomics technologies for PCa biomarker development, such as enhancing the detection sensitivity of low-abundance proteins through antibody-based or antibody-independent protein/peptide enrichment, enriching post-translational modifications such as glycosylation as well as information-rich extracellular vesicles, and increasing accuracy and throughput using advanced data acquisition methodologies. This chapter also summarizes recent PCa biomarker validation studies that applied those techniques in diverse specimen types, including cell lines, tissues, proximal fluids, urine, and blood, developing novel protein biomarkers for various clinical applications, including early detection and diagnosis, prognosis, and therapeutic intervention of PCa.</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":"141736295","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}
Pub Date : 2024-01-01Epub Date: 2024-05-22DOI: 10.1016/bs.acr.2024.05.001
Gunjan Purohit, Polash Ghosh, Oleh Khalimonchuk
Our understanding of the roles that mitochondria play in cellular physiology has evolved drastically-from a mere cellular energy supplier to a crucial regulator of metabolic and signaling processes, particularly in the context of development and progression of human diseases such as cancers. The present review examines the role of OMA1, a conserved, redox-sensitive metallopeptidase in cancer biology. OMA1's involvement in mitochondrial quality control, redox activity, and stress responses underscores its potential as a novel target in cancer diagnosis and treatment. However, our incomplete understanding of OMA1's regulation and structural detail presents ongoing challenges to target OMA1 for therapeutic purposes. Further exploration of OMA1 holds promise in uncovering novel insights into cancer mechanisms and therapeutic strategies. In this chapter, we briefly summarize our current knowledge about OMA1, its redox-regulation, and emerging role in certain cancers.
{"title":"Mitochondrial metallopeptidase OMA1 in cancer.","authors":"Gunjan Purohit, Polash Ghosh, Oleh Khalimonchuk","doi":"10.1016/bs.acr.2024.05.001","DOIUrl":"10.1016/bs.acr.2024.05.001","url":null,"abstract":"<p><p>Our understanding of the roles that mitochondria play in cellular physiology has evolved drastically-from a mere cellular energy supplier to a crucial regulator of metabolic and signaling processes, particularly in the context of development and progression of human diseases such as cancers. The present review examines the role of OMA1, a conserved, redox-sensitive metallopeptidase in cancer biology. OMA1's involvement in mitochondrial quality control, redox activity, and stress responses underscores its potential as a novel target in cancer diagnosis and treatment. However, our incomplete understanding of OMA1's regulation and structural detail presents ongoing challenges to target OMA1 for therapeutic purposes. Further exploration of OMA1 holds promise in uncovering novel insights into cancer mechanisms and therapeutic strategies. In this chapter, we briefly summarize our current knowledge about OMA1, its redox-regulation, and emerging role in certain 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":"141790737","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}
Pub Date : 2024-01-01DOI: 10.1016/S0065-230X(24)00038-1
O John Semmes, Julius O Nyalwidhe, Swadesh K Das, Paul B Fisher
{"title":"Preface.","authors":"O John Semmes, Julius O Nyalwidhe, Swadesh K Das, Paul B Fisher","doi":"10.1016/S0065-230X(24)00038-1","DOIUrl":"https://doi.org/10.1016/S0065-230X(24)00038-1","url":null,"abstract":"","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":"141736296","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}
Prostate cancer is one of the most common malignancies among men worldwide. Besides genetic alterations, epigenetic modulations including DNA methylation, histone modifications and miRNA mediated alteration of gene expression are the key driving forces for the prostate tumor development and cancer progression. Aberrant expression and/or the activity of the epigenetic modifiers/enzymes, results in aberrant expression of genes involved in DNA repair, cell cycle regulation, cell adhesion, apoptosis, autophagy, tumor suppression and hormone response and thereby disease progression. Altered epigenome is associated with prostate cancer recurrence, progression, aggressiveness and transition from androgen-dependent to androgen-independent phenotype. These epigenetic modifications are reversible and various compounds/drugs targeting the epigenetic enzymes have been developed that are effective in cancer treatment. This chapter focuses on the epigenetic alterations in prostate cancer initiation and progression, listing different epigenetic biomarkers for diagnosis and prognosis of the disease and their potential as therapeutic targets. This chapter also summarizes different epigenetic drugs approved for prostate cancer therapy and the drugs available for clinical trials.
前列腺癌是全球男性最常见的恶性肿瘤之一。除基因改变外,包括 DNA 甲基化、组蛋白修饰和 miRNA 介导的基因表达改变在内的表观遗传修饰是前列腺肿瘤发生和癌症进展的主要驱动力。表观遗传修饰因子/酶的异常表达和/或活性导致参与 DNA 修复、细胞周期调控、细胞粘附、细胞凋亡、自噬、肿瘤抑制和激素反应的基因异常表达,从而导致疾病进展。表观基因组的改变与前列腺癌的复发、进展、侵袭性以及从依赖雄激素表型向不依赖雄激素表型的转变有关。这些表观遗传修饰是可逆的,目前已开发出多种针对表观遗传酶的化合物/药物,可有效治疗癌症。本章重点介绍前列腺癌发生和发展过程中的表观遗传学改变,列出用于诊断和预后的不同表观遗传学生物标志物及其作为治疗靶点的潜力。本章还总结了已批准用于前列腺癌治疗的不同表观遗传药物以及可用于临床试验的药物。
{"title":"Epigenetic regulation of androgen dependent and independent prostate cancer.","authors":"Jagdish Mishra, Subhajit Chakraborty, Piyasa Nandi, Soumen Manna, Tirthankar Baral, Niharika, Ankan Roy, Prahallad Mishra, Samir Kumar Patra","doi":"10.1016/bs.acr.2024.05.007","DOIUrl":"https://doi.org/10.1016/bs.acr.2024.05.007","url":null,"abstract":"<p><p>Prostate cancer is one of the most common malignancies among men worldwide. Besides genetic alterations, epigenetic modulations including DNA methylation, histone modifications and miRNA mediated alteration of gene expression are the key driving forces for the prostate tumor development and cancer progression. Aberrant expression and/or the activity of the epigenetic modifiers/enzymes, results in aberrant expression of genes involved in DNA repair, cell cycle regulation, cell adhesion, apoptosis, autophagy, tumor suppression and hormone response and thereby disease progression. Altered epigenome is associated with prostate cancer recurrence, progression, aggressiveness and transition from androgen-dependent to androgen-independent phenotype. These epigenetic modifications are reversible and various compounds/drugs targeting the epigenetic enzymes have been developed that are effective in cancer treatment. This chapter focuses on the epigenetic alterations in prostate cancer initiation and progression, listing different epigenetic biomarkers for diagnosis and prognosis of the disease and their potential as therapeutic targets. This chapter also summarizes different epigenetic drugs approved for prostate cancer therapy and the drugs available for clinical trials.</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":"141736278","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}
Pub Date : 2024-01-01Epub Date: 2024-06-12DOI: 10.1016/bs.acr.2024.05.008
Caleb Smack, Benjamin Johnson, Julius O Nyalwidhe, O John Semmes, Lifang Yang
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.
{"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}
Pub Date : 2024-01-01Epub Date: 2024-07-02DOI: 10.1016/bs.acr.2024.06.004
Therese Featherston, Martina Paumann-Page, Mark B Hampton
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.
{"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}
Pub Date : 2024-01-01Epub Date: 2024-04-27DOI: 10.1016/bs.acr.2024.04.004
Asit K Paul, John W Melson, Samina Hirani, Selvaraj Muthusamy
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.
{"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}