Pub Date : 2025-11-06DOI: 10.1016/j.cpt.2025.11.001
Jiaen You , Zebing Liu , Kang He
Primary cardiac tumors are rare and often present diagnostic challenges due to their non-specific symptoms and imaging characteristics. In this report, we present a case of right atrial intimal sarcoma (IS) with liver metastasis. A 49-year-old woman presented to the emergency department with acute dyspnea, cyanosis, nausea, vomiting, and upper abdominal pain. Echocardiography revealed a large pericardial effusion and a mass in the right atrium. Contrast-enhanced computed tomography (CT) and positron emission tomography/CT (PET/CT) confirmed the presence of multiple nodules in the right atrium and hepatic masses, suggesting metastatic disease. Laboratory tests indicated liver dysfunction, with elevated carbohydrate antigen 125 (CA125) and normal alpha-fetoprotein (AFP) levels. These clinical features initially suggested a diagnosis of hepatocellular carcinoma with isolated cardiac metastasis. However, the final pathological examination and gene sequencing results were unexpected, leading to the diagnosis of right atrial IS with liver metastasis. The patient was managed conservatively and remained alive for 8 months at the time of manuscript submission.
{"title":"Right atrial intimal sarcoma with liver metastasis: A case report and literature review","authors":"Jiaen You , Zebing Liu , Kang He","doi":"10.1016/j.cpt.2025.11.001","DOIUrl":"10.1016/j.cpt.2025.11.001","url":null,"abstract":"<div><div>Primary cardiac tumors are rare and often present diagnostic challenges due to their non-specific symptoms and imaging characteristics. In this report, we present a case of right atrial intimal sarcoma (IS) with liver metastasis. A 49-year-old woman presented to the emergency department with acute dyspnea, cyanosis, nausea, vomiting, and upper abdominal pain. Echocardiography revealed a large pericardial effusion and a mass in the right atrium. Contrast-enhanced computed tomography (CT) and positron emission tomography/CT (PET/CT) confirmed the presence of multiple nodules in the right atrium and hepatic masses, suggesting metastatic disease. Laboratory tests indicated liver dysfunction, with elevated carbohydrate antigen 125 (CA125) and normal alpha-fetoprotein (AFP) levels. These clinical features initially suggested a diagnosis of hepatocellular carcinoma with isolated cardiac metastasis. However, the final pathological examination and gene sequencing results were unexpected, leading to the diagnosis of right atrial IS with liver metastasis. The patient was managed conservatively and remained alive for 8 months at the time of manuscript submission.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 2","pages":"Pages 158-161"},"PeriodicalIF":2.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078480","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 : 2025-10-24DOI: 10.1016/j.cpt.2025.10.001
Xingyao Lyu , Bixia Li , Zhijie Lin
Cancer immunotherapy has emerged as a promising complement to traditional treatments such as radiotherapy and chemotherapy. Although conventional therapies remain central to cancer management, the potential of immunotherapy is increasingly recognized. Immune checkpoint therapy, a key strategy in tumor immunotherapy, has demonstrated significant efficacy against solid tumors. However, its clinical application is hindered by its limited response rate, necessitating efforts to optimize its effectiveness. Recent studies have highlighted the pivotal role of the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon gene (STING) pathway in immune checkpoint therapy. Manganese (Mn), an essential trace element, regulates the activity of CD8+ T and NK cells by modulating the cGAS-STING pathway. Furthermore, the combination of Mn with anti-programmed cell death protein 1 therapy has demonstrated promising anti-tumor effects. Mn also influences immunogenic cell death (ICD), further augmenting its potential as an adjunct to tumor immunotherapy. Despite a growing body of research on the role of Mn in modulating the cGAS-STING pathway and inducing ICD, comprehensive reviews that synthesize these findings and explore the potential of Mn in enhancing immune checkpoint therapy are still lacking. This review aimed to fill this gap by examining the immune mechanisms by which Mn enhances immune checkpoint therapy and its overall impact on tumor immunotherapy.
{"title":"Targeting immune checkpoint therapy: The role of manganese in tumor immunotherapy","authors":"Xingyao Lyu , Bixia Li , Zhijie Lin","doi":"10.1016/j.cpt.2025.10.001","DOIUrl":"10.1016/j.cpt.2025.10.001","url":null,"abstract":"<div><div>Cancer immunotherapy has emerged as a promising complement to traditional treatments such as radiotherapy and chemotherapy. Although conventional therapies remain central to cancer management, the potential of immunotherapy is increasingly recognized. Immune checkpoint therapy, a key strategy in tumor immunotherapy, has demonstrated significant efficacy against solid tumors. However, its clinical application is hindered by its limited response rate, necessitating efforts to optimize its effectiveness. Recent studies have highlighted the pivotal role of the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon gene (STING) pathway in immune checkpoint therapy. Manganese (Mn), an essential trace element, regulates the activity of CD8<sup>+</sup> T and NK cells by modulating the cGAS-STING pathway. Furthermore, the combination of Mn with anti-programmed cell death protein 1 therapy has demonstrated promising anti-tumor effects. Mn also influences immunogenic cell death (ICD), further augmenting its potential as an adjunct to tumor immunotherapy. Despite a growing body of research on the role of Mn in modulating the cGAS-STING pathway and inducing ICD, comprehensive reviews that synthesize these findings and explore the potential of Mn in enhancing immune checkpoint therapy are still lacking. This review aimed to fill this gap by examining the immune mechanisms by which Mn enhances immune checkpoint therapy and its overall impact on tumor immunotherapy.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 3","pages":"Pages 165-173"},"PeriodicalIF":2.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161692","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 : 2025-08-29DOI: 10.1016/j.cpt.2025.08.005
Haitao Tao , Yining Liu , Lijie Wang , Jinliang Wang , Junxun Ma , Guoqing Zhang , Zhefeng Liu , Yi Hu
Background
Immune checkpoint inhibitors combined with PARP inhibitors and chemotherapy can enhance anti-tumor activity. This phase Ib clinical study was designed to evaluate the safety and efficacy of cisplatin in combination with sintilimab and niraparib in patients with advanced solid tumors.
Methods
Patients with advanced solid tumors who had progressed after one or more lines of standard therapy were enrolled in the study, and received cisplatin and sintilimab on day 1 and niraparib from days 1–21 every 3 weeks for up to 4 cycles, followed by maintenance therapy with sintilimab and niraparib (the same doses and schedules as before), until disease progression, death, or intolerable toxicities. During the dose-escalation phase, patients were divided into three dose groups on the basis of a 3 + 3 dose-escalation regimen, and a dose-expansion phase was conducted based on the determined maximum tolerated dose (MTD). The primary endpoint was safety, including treatment-related adverse events (TRAEs), dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D), and the secondary endpoint was efficacy. In addition, exploratory endpoints were prespecified to analyze potential biomarkers.
Results
From July 31, 2019, to July 1, 2022, a total of 26 patients were enrolled, and no DLTs were observed in the dose-escalation phase. The recommended RP2Ds of cisplatin, sintilimab, and niraparib were 60 mg/m2, 200 mg, and 100 mg every 3 weeks, respectively. All patients experienced TRAEs of varying severity, and a 19.23% (5 patients) incidence of immune-related adverse events (irAEs). With the median follow-up time of 47.9 months (95% CI: 38.8–NA), objective response rate was 26.92% (7 patients, 95% confidence interval [CI], 11.57–47.79), disease control rate was 57.69% (15 patients, 95% CI: 36.92–76.65), the median progression-free survival (PFS) was 3.30 months (95% CI: 2.14–4.46) and the median overall survival (OS) was 8.03 months (95% CI: 3.41–12.66), with PFS rates of 26.92% (seven patients) and 11.54% (three patients) at 6 and 12 months, and OS rates of 69.23%, 34.62% and 11.54% at 6, 12 and 24 months, respectively. Patients with programmed cell death ligand 1 (PD-L1) expression ≥ 1% showed significantly longer PFS (3.93 months, P = 0.032) and OS (14.97 months, P = 0.036) compared to those with PD-L1 expression < 1%.
Conclusion
The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in patients with advanced solid tumors. Further validation in larger, histology-specific patients is needed to confirm clinical benefit.
{"title":"Safety and efficacy of Cisplatin in combination with Sintilimab and Niraparib in patients with advanced solid tumors: A phase Ib study","authors":"Haitao Tao , Yining Liu , Lijie Wang , Jinliang Wang , Junxun Ma , Guoqing Zhang , Zhefeng Liu , Yi Hu","doi":"10.1016/j.cpt.2025.08.005","DOIUrl":"10.1016/j.cpt.2025.08.005","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors combined with PARP inhibitors and chemotherapy can enhance anti-tumor activity. This phase Ib clinical study was designed to evaluate the safety and efficacy of cisplatin in combination with sintilimab and niraparib in patients with advanced solid tumors.</div></div><div><h3>Methods</h3><div>Patients with advanced solid tumors who had progressed after one or more lines of standard therapy were enrolled in the study, and received cisplatin and sintilimab on day 1 and niraparib from days 1–21 every 3 weeks for up to 4 cycles, followed by maintenance therapy with sintilimab and niraparib (the same doses and schedules as before), until disease progression, death, or intolerable toxicities. During the dose-escalation phase, patients were divided into three dose groups on the basis of a 3 + 3 dose-escalation regimen, and a dose-expansion phase was conducted based on the determined maximum tolerated dose (MTD). The primary endpoint was safety, including treatment-related adverse events (TRAEs), dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D), and the secondary endpoint was efficacy. In addition, exploratory endpoints were prespecified to analyze potential biomarkers.</div></div><div><h3>Results</h3><div>From July 31, 2019, to July 1, 2022, a total of 26 patients were enrolled, and no DLTs were observed in the dose-escalation phase. The recommended RP2Ds of cisplatin, sintilimab, and niraparib were 60 mg/m<sup>2</sup>, 200 mg, and 100 mg every 3 weeks, respectively. All patients experienced TRAEs of varying severity, and a 19.23% (5 patients) incidence of immune-related adverse events (irAEs). With the median follow-up time of 47.9 months (95% CI: 38.8–NA), objective response rate was 26.92% (7 patients, 95% confidence interval [CI], 11.57–47.79), disease control rate was 57.69% (15 patients, 95% CI: 36.92–76.65), the median progression-free survival (PFS) was 3.30 months (95% CI: 2.14–4.46) and the median overall survival (OS) was 8.03 months (95% CI: 3.41–12.66), with PFS rates of 26.92% (seven patients) and 11.54% (three patients) at 6 and 12 months, and OS rates of 69.23%, 34.62% and 11.54% at 6, 12 and 24 months, respectively. Patients with programmed cell death ligand 1 (PD-L1) expression ≥ 1% showed significantly longer PFS (3.93 months, <em>P</em> = 0.032) and OS (14.97 months, <em>P</em> = 0.036) compared to those with PD-L1 expression < 1%.</div></div><div><h3>Conclusion</h3><div>The combination of cisplatin with sintilimab and niraparib showed a manageable safety profile and modest anti-tumor activity in patients with advanced solid tumors. Further validation in larger, histology-specific patients is needed to confirm clinical benefit.</div></div><div><h3>Trial registration</h3><div><span><span>https://www.chictr.org.cn/</span><svg><path></path></svg></span>; ID: ChiCTR1900024488.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 1","pages":"Pages 41-50"},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618290","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}
Marine-derived compounds have emerged as a promising frontier in cancer research due to their remarkable structural diversity and broad-spectrum bioactivities. The marine environment, encompassing diverse organisms (e.g., sponges, algae, tunicates, mollusks, and marine microbes), is a prolific source of novel bioactive molecules with potent anti-cancer properties. Key classes of these compounds include alkaloids, polysaccharides, peptides, terpenoids, and polyketides, which exert anti-tumor effects through diverse mechanisms, including the induction of apoptosis, inhibition of angiogenesis, modulation of immune responses, interference with cell cycle progression, and targeting of critical signaling pathways involved in tumorigenesis and metastasis. Notably, marine-derived drugs such as trabectedin, eribulin, and plitidepsin have received regulatory approval for the treatment of various malignancies, demonstrating the translational potential of these natural compounds. Ongoing clinical and preclinical investigations are exploring a wide range of marine metabolites for their cytotoxic, anti-proliferative, and chemosensitizing properties. Advances in marine biotechnology, including genome mining, synthetic biology, and fermentation technologies, have significantly facilitated the discovery, sustainable production, and structural optimization of marine natural products. However, challenges such as low yield, structural complexity, limited water solubility, and poor bioavailability hinder their broader clinical application. The integration of novel drug delivery systems, such as nanoparticles, liposomes, and conjugates, offers a viable solution to overcome these limitations and improve pharmacokinetic profiles. This review provides a comprehensive overview of the mechanisms of action, therapeutic applications, and clinical development of marine-derived anti-cancer compounds. It also emphasizes the need for deeper insights into their molecular targets and the potential for synergistic use with existing chemotherapeutic agents. Future directions should focus on exploring untapped marine biodiversity, developing eco-friendly harvesting strategies, and developing innovative delivery platforms to fully harness the therapeutic promise of the marine pharmacopeia in oncology.
{"title":"Exploring marine-derived compounds as potential anti-cancer agents: Mechanisms and therapeutic implications","authors":"Nagaraju Bandaru , Yash Pramod Patil , Sumit Dilip Ekghara , Kunal Sharad patil , Mohan Gandhi Bonthu","doi":"10.1016/j.cpt.2025.08.004","DOIUrl":"10.1016/j.cpt.2025.08.004","url":null,"abstract":"<div><div>Marine-derived compounds have emerged as a promising frontier in cancer research due to their remarkable structural diversity and broad-spectrum bioactivities. The marine environment, encompassing diverse organisms (e.g., sponges, algae, tunicates, mollusks, and marine microbes), is a prolific source of novel bioactive molecules with potent anti-cancer properties. Key classes of these compounds include alkaloids, polysaccharides, peptides, terpenoids, and polyketides, which exert anti-tumor effects through diverse mechanisms, including the induction of apoptosis, inhibition of angiogenesis, modulation of immune responses, interference with cell cycle progression, and targeting of critical signaling pathways involved in tumorigenesis and metastasis. Notably, marine-derived drugs such as trabectedin, eribulin, and plitidepsin have received regulatory approval for the treatment of various malignancies, demonstrating the translational potential of these natural compounds. Ongoing clinical and preclinical investigations are exploring a wide range of marine metabolites for their cytotoxic, anti-proliferative, and chemosensitizing properties. Advances in marine biotechnology, including genome mining, synthetic biology, and fermentation technologies, have significantly facilitated the discovery, sustainable production, and structural optimization of marine natural products. However, challenges such as low yield, structural complexity, limited water solubility, and poor bioavailability hinder their broader clinical application. The integration of novel drug delivery systems, such as nanoparticles, liposomes, and conjugates, offers a viable solution to overcome these limitations and improve pharmacokinetic profiles. This review provides a comprehensive overview of the mechanisms of action, therapeutic applications, and clinical development of marine-derived anti-cancer compounds. It also emphasizes the need for deeper insights into their molecular targets and the potential for synergistic use with existing chemotherapeutic agents. Future directions should focus on exploring untapped marine biodiversity, developing eco-friendly harvesting strategies, and developing innovative delivery platforms to fully harness the therapeutic promise of the marine pharmacopeia in oncology.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 3","pages":"Pages 192-207"},"PeriodicalIF":2.8,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161743","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 : 2025-07-12DOI: 10.1016/j.cpt.2025.07.003
Abdul Halim Shaikat , S.M. Asadul Karim Azad , Md Azizur Rahman Tamim , Mohammed Sailim Ullah , Mohammad Nurul Amin , Mofazzal K. Sabbir , Md Towhidul Islam Tarun , Md Saqline Mostaq , Shohana Sabrin , Md Zihad Mahmud , Md Ashiq Mahmud
Hypoxia, a hallmark of the tumor microenvironment (TME), drives cancer progression through immune modulation, angiogenesis promotion, metabolic reprogramming, and uncontrolled cell proliferation. This review explores the diverse functions of hypoxia-inducible factor (HIF) signaling in cancer development and progression, providing a comprehensive overview of the molecular pathways. HIFs, particularly HIF-1α and HIF-2α, regulate several genes related to cancer hallmarks such as invasion, metabolic reprogramming, angiogenesis, and therapy resistance, thus mediating a significant portion of the hypoxic response. Hydroxylation of proline and asparagine residues in HIF-α subunits, which occurs in an oxygen-dependent manner, serves as a key regulatory mechanism for both their stability and transcriptional function. Notably, this complex interaction is regulated by multiple signaling pathways, including the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. In cancer, HIF signaling affects several aspects of tumor cell biology that contribute to the cancerous characteristics, including angiogenesis induction through the upregulation of vascular endothelial growth factor (VEGF) expression, metabolic reprogramming through the enhancement of the Warburg effect, facilitation of cancer invasion and metastasis by driving epithelial-to-mesenchymal transition (EMT) and matrix remodeling patterns, and mediation of therapeutic resistance partly due to the effects on drug efflux pumps and DNA damage repair. Direct and indirect HIF inhibitors—including small molecules, peptidomimetics, antibodies, and proteolysis-targeting chimeras (PROTACs)—are under preclinical and clinical evaluation for their therapeutic efficacy. Preclinical and early clinical trials have demonstrated significant synergistic effects in inhibiting tumor development when HIF inhibition is combined with traditional therapies (chemotherapy or radiation) or immunotherapies, emphasizing major clinical implications and the potential for improving patient outcomes. Although challenges exist, particularly regarding drug resistance, further research to improve therapeutic efficacy and prolong survival for patients is warranted.
{"title":"Investigating hypoxia-inducible factor signaling in cancer: Mechanisms, clinical implications, targeted therapeutic strategies, and resistance","authors":"Abdul Halim Shaikat , S.M. Asadul Karim Azad , Md Azizur Rahman Tamim , Mohammed Sailim Ullah , Mohammad Nurul Amin , Mofazzal K. Sabbir , Md Towhidul Islam Tarun , Md Saqline Mostaq , Shohana Sabrin , Md Zihad Mahmud , Md Ashiq Mahmud","doi":"10.1016/j.cpt.2025.07.003","DOIUrl":"10.1016/j.cpt.2025.07.003","url":null,"abstract":"<div><div>Hypoxia, a hallmark of the tumor microenvironment (TME), drives cancer progression through immune modulation, angiogenesis promotion, metabolic reprogramming, and uncontrolled cell proliferation. This review explores the diverse functions of hypoxia-inducible factor (HIF) signaling in cancer development and progression, providing a comprehensive overview of the molecular pathways. HIFs, particularly HIF-1α and HIF-2α, regulate several genes related to cancer hallmarks such as invasion, metabolic reprogramming, angiogenesis, and therapy resistance, thus mediating a significant portion of the hypoxic response. Hydroxylation of proline and asparagine residues in HIF-α subunits, which occurs in an oxygen-dependent manner, serves as a key regulatory mechanism for both their stability and transcriptional function. Notably, this complex interaction is regulated by multiple signaling pathways, including the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. In cancer, HIF signaling affects several aspects of tumor cell biology that contribute to the cancerous characteristics, including angiogenesis induction through the upregulation of vascular endothelial growth factor (VEGF) expression, metabolic reprogramming through the enhancement of the Warburg effect, facilitation of cancer invasion and metastasis by driving epithelial-to-mesenchymal transition (EMT) and matrix remodeling patterns, and mediation of therapeutic resistance partly due to the effects on drug efflux pumps and DNA damage repair. Direct and indirect HIF inhibitors—including small molecules, peptidomimetics, antibodies, and proteolysis-targeting chimeras (PROTACs)—are under preclinical and clinical evaluation for their therapeutic efficacy. Preclinical and early clinical trials have demonstrated significant synergistic effects in inhibiting tumor development when HIF inhibition is combined with traditional therapies (chemotherapy or radiation) or immunotherapies, emphasizing major clinical implications and the potential for improving patient outcomes. Although challenges exist, particularly regarding drug resistance, further research to improve therapeutic efficacy and prolong survival for patients is warranted.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 3","pages":"Pages 174-191"},"PeriodicalIF":2.8,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161694","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 : 2025-07-08DOI: 10.1016/j.cpt.2025.07.002
Yaguang Peng , Peng Lyu , Xiaoxia Peng
{"title":"Improving research transparency: An interpretation of the updated consolidated standards of reporting trials 2025 guideline from the perspective of clinical trials in oncology","authors":"Yaguang Peng , Peng Lyu , Xiaoxia Peng","doi":"10.1016/j.cpt.2025.07.002","DOIUrl":"10.1016/j.cpt.2025.07.002","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 1","pages":"Pages 75-80"},"PeriodicalIF":2.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790124","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 : 2025-07-05DOI: 10.1016/j.cpt.2025.06.008
Zhuocheng Lai , Chenxi Hu , Jirong Jie , Yongyuan Xiao , Yuanchao Zhu , Xueni Guo , Yintong Liu , Yiwei Wang , Shiyu Pang , Xiangbo Zeng , Wanlong Tan , Qiong Wang
Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer (CRPC) that is typically resistant to nearly all current therapies. In this study, single-cell RNA sequencing (scRNA-seq) and dataset analyses identified Centrosomal Protein 55 (CEP55) as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately to, NEPC. Subsequent bioinformatics analyses and validation with clinical samples demonstrated that CEP55 is significantly upregulated in NEPC tissues compared to HSPC and CRPC. Furthermore, while CEP55 show no significant association with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby driving NEPC progression. Specifically, in vivo and in vitro experiments confirmed that CEP55 enhances cell proliferation, migration, invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, CEP55 has been shown to regulate cisplatin resistance through the phosphorylation of CDK1 at the tyrosine 15 (Tyr15) site. In summary, our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer, suggesting its potential as an important therapeutic target.
{"title":"Neuroendocrine prostate cancer (NEPC)-associated CEP55 promotes cisplatin resistance in prostate cancer by regulating CDK1 phosphorylation","authors":"Zhuocheng Lai , Chenxi Hu , Jirong Jie , Yongyuan Xiao , Yuanchao Zhu , Xueni Guo , Yintong Liu , Yiwei Wang , Shiyu Pang , Xiangbo Zeng , Wanlong Tan , Qiong Wang","doi":"10.1016/j.cpt.2025.06.008","DOIUrl":"10.1016/j.cpt.2025.06.008","url":null,"abstract":"<div><div>Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer (CRPC) that is typically resistant to nearly all current therapies. In this study, single-cell RNA sequencing (scRNA-seq) and dataset analyses identified Centrosomal Protein 55 (<em>CEP55</em>) as a critical factor in the transformation from hormone-sensitive prostate cancer (HSPC) to CRPC and, ultimately to, NEPC. Subsequent bioinformatics analyses and validation with clinical samples demonstrated that <em>CEP55</em> is significantly upregulated in NEPC tissues compared to HSPC and CRPC. Furthermore, while <em>CEP55</em> show no significant association with the immune microenvironment or cancer-associated fibroblasts (CAFs), our findings indicate that it directly mediates the plasticity of prostate cancer cells, thereby driving NEPC progression. Specifically, <em>in vivo</em> and <em>in vitro</em> experiments confirmed that <em>CEP55</em> enhances cell proliferation, migration, invasion and the expression of NEPC biomarkers in prostate cancer. Importantly, although cisplatin is the primary treatment for NEPC clinically, <em>CEP55</em> has been shown to regulate cisplatin resistance through the phosphorylation of CDK1 at the tyrosine 15 (Tyr15) site. In summary, our study identifies a key gene that influences the neuroendocrine differentiation process in prostate cancer, suggesting its potential as an important therapeutic target.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"4 1","pages":"Pages 51-63"},"PeriodicalIF":2.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145618291","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}
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