Cancer Biology & Therapy最新文献

{"title":"First-line treatments for KRAS-mutant non-small cell lung cancer: current state and future perspectives.","authors":"Qi He, Xiaoyan Liu, Liyan Jiang, Ping Liu, Weixia Xuan, Yudong Wang, Rui Meng, Huijing Feng, Shuang Lv, Qian Miao, Di Zheng, Yan Xu, Mengzhao Wang","doi":"10.1080/15384047.2024.2441499","DOIUrl":"10.1080/15384047.2024.2441499","url":null,"abstract":"<p><p><i>KRAS</i> mutations are common in non-small cell lung cancer (NSCLC) and are associated with patient prognosis; however, targeting <i>KRAS</i> has faced various difficulties. Currently, immunotherapy, chemotherapy, and chemoimmunotherapy play pivotal roles in the first-line treatment of <i>KRAS</i>-mutated NSCLC. Here, we summarize the current evidence on first-line therapies and compare the treatment outcomes and biomarkers for different regimens. KRAS inhibitors and other emerging alternative treatments are also discussed, as combining these drugs with immunotherapy may serve as a promising first-line treatment for <i>KRAS</i>-mutated NSCLC in the future. We hope that this review will assist in first-line treatment choices and shed light on the development of novel agents for <i>KRAS</i>-mutated NSCLC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2441499"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of NDUFAF6 inhibits breast cancer progression via promoting mitophagy and apoptosis.","authors":"Shang Wu, Xindi Ma, Xiangmei Zhang, Kaiye Du, Chao Shi, Ahmed Ali Almaamari, Boye Han, Suwen Su, Yunjiang Liu","doi":"10.1080/15384047.2024.2445220","DOIUrl":"https://doi.org/10.1080/15384047.2024.2445220","url":null,"abstract":"<p><strong>Background: </strong>While NDUFAF6 is implicated in breast cancer, its specific role remains unclear.</p><p><strong>Methods: </strong>The expression levels and prognostic significance of NDUFAF6 in breast cancer were assessed using The Cancer Genome Atlas, Gene Expression Omnibus, Kaplan-Meier plotter and cBio-Portal databases. We knocked down NDUFAF6 in breast cancer cells using small interfering RNA and investigated its effects on cell proliferation and migration ability. We performed gene expression analysis and validated key findings using protein analysis. We also assessed mitochondrial activity and cellular metabolism.</p><p><strong>Results: </strong>NDUFAF6 was highly expressed in breast cancer, which was associated with a poorer prognosis. Knockdown of NDUFAF6 reduced the proliferation and migration ability of breast cancer cells. Transcriptome analysis revealed 2,101 differentially expressed genes enriched in apoptosis and mitochondrial signaling pathways. Western blot results showed NDUFAF6 knockdown enhanced apoptosis. In addition, differential gene enrichment analysis was related to mitochondrial signaling pathways, and western blot results verified that mitophagy was enhanced in NDUFAF6 knockdown breast cancer cells. JC-1 assay also showed that mitochondrial dysfunction and reactive oxygen species content were increased after knocking down NDUFAF6. In addition, basal and maximal mitochondrial oxygen consumption decreased, and intracellular glycogen content increased.</p><p><strong>Conclusions: </strong>Knockdown of NDUFAF6 resulted in apoptosis and mitophagy in breast cancer cells and NDUFAF6 may be a potential molecular target for breast cancer therapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2445220"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RNA-binding protein ELAVL1 promotes Beclin1-mediated cellular autophagy and thus endometrial cancer development by affecting LncRNA-neat stability.","authors":"Yanlu Luo, Xueyan Zhong, Xinzhao Sun, Jiangtao Fan","doi":"10.1080/15384047.2025.2469927","DOIUrl":"10.1080/15384047.2025.2469927","url":null,"abstract":"<p><p>Our study aims to investigate the roles of embryonic lethal abnormal vision-like 1 (ELAVL1) and long non-coding RNA (LncRNA) NEAT1 in endometrial cancer (EC), focusing on their underlying molecular mechanisms.We obtained EC cell lines (HEC-1A, Ishikawa, RL95-2, HEC-1B, and AN3CA) from ATCC. We used siRNAs (si-ELAVL1#1 and si-ELAVL1#2) and overexpression RNAs (OE ELAVL1 and OE-NEAT1) for knockdown or overexpression of ELAVL1 and LncRNA NEAT1. We also employed 3-MA (5mM) or rapamycin (100µM) to inhibit or promote autophagy. Moreover, we conducted RNA immunoprecipitation (RIP) assays to confirm the interaction between LncRNA NEAT1 and ELAVL1. Cell Counting Kit-8 (CCK-8) and transwell assays were utilized to assess cell proliferation and migration. Additionally, we measured the expression of ELAVL1 and Beclin1 through Western blotting and RT-qPCR.ELAVL1 was found to be highly expressed in EC. Furthermore, ELAVL1 promoted the proliferation, invasion, and migration of EC cells through the regulation of Beclin1-related pathways. RIP assays revealed a direct interaction between LncRNA NEAT1 and ELAVL1, with ELAVL1 stabilizing LncRNA NEAT1 mRNA in EC cells. Additionally, we observed that ELAVL1 influenced EC cell proliferation, invasion, and migration through the regulation of LncRNA NEAT1-mediated regulation of Beclin1 expression. Moreover, in an animal study, we determined that ELAVL1 influenced endometrial cancer tumor growth through its interaction with LncRNA NEAT1, which mediated Beclin1 expression in vivo.In summary, our study showed that ELAVL1 regulated the malignant behavior of endometrial cancer cells through the modulation of LncRNA NEAT1-mediated regulation of Beclin1 expression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2469927"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mitochondria as an emerging target of self-renewal in T-cell acute lymphoblastic leukemia.","authors":"Majd A Al-Hamaly, Evelyn Winter, Jessica S Blackburn","doi":"10.1080/15384047.2025.2460252","DOIUrl":"10.1080/15384047.2025.2460252","url":null,"abstract":"<p><p>Acute lymphocytic leukemia (ALL) is the most common leukemia in children, with the T-cell subtype (T-ALL) accounting for 15% of those cases. Despite advancements in the treatment of T-ALL, patients still face a dismal prognosis following their first relapse. Relapse can be attributed to the inability of chemotherapy agents to eradicate leukemia stem cells (LSC), which possess self-renewal capabilities and are responsible for the long-term maintenance of the disease. Mitochondria have been recognized as a therapeutic vulnerability for cancer stem cells, including LSCs. Mitocans have shown promise in T-ALL both <i>in vitro</i> and <i>in vivo</i>, with some currently in early-phase clinical trials. However, due to challenges in studying LSCs in T-ALL, our understanding of how mitochondrial function influences self-renewal remains limited. This review highlights the emerging literature on targeting mitochondria in diverse T-ALL models, emphasizing specific mitochondrial vulnerabilities linked to LSC self-renewal and their potential to significantly improve T-ALL treatment.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2460252"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML.","authors":"Zhanglin Zhang, Xiang Lin, Yaling Yang, Xuemei Wang, Yi Wang, Xianbao Huang, Miao Hong, Wei Gao, Hua He, M James You, Yi Yang, Guangyao Kong","doi":"10.1080/15384047.2025.2459426","DOIUrl":"10.1080/15384047.2025.2459426","url":null,"abstract":"<p><p>Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development of multiple cancers. Targeted regulation of deubiquitination has been recognized as an important strategy in tumor therapy. However, the mechanism by which drugs regulate deubiquitinase is not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member of the ubiquitin-specific protease family highly expressed in various tumors, as a specific substrate for the activated caspase-3. During drug induced apoptosis of AML cells, activated caspase-3 cleaves USP48 through recognizing the conservative motif DEQD located at 611-614 sites of human USP48. Subsequent analysis showed that the cleavage USP48 N-terminal fragment which contains catalytic active domain is easily degraded by ubiquitination. Meanwhile knockdown experiment showed that inhibiting the expression of USP48 could also promotes apoptosis and enhance the efficacy of chemotherapy drugs. Altogether, these results suggest that targeting USP48 may represent a novel therapeutic strategy in AML.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2459426"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-301a-mediated crosstalk between the Hedgehog and HIPPO/YAP signaling pathways promotes pancreatic cancer.","authors":"Bing Qi, Yuqiong Wang, Xian Zhu, Yanfang Gong, Jing Jin, Hongyu Wu, Xiaohua Man, Feng Liu, Wenzhu Yao, Jun Gao","doi":"10.1080/15384047.2025.2457761","DOIUrl":"10.1080/15384047.2025.2457761","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge in oncology due to its dismal prognosis and limited therapeutic options. In this study, we investigated the role of miR-301a in facilitating crosstalk between the Hedgehog (Hh) and HIPPO/YAP signaling pathways during the progression of PDAC. Our findings revealed that miR-301a served as a central regulatory node, targeting Gli1 within the Hh pathway and STK4 within the HIPPO/YAP pathway. Immunohistochemical and molecular analyses confirmed dysregulation of pathway components in pancreatic cancer, underscoring the pivotal role of miR-301a. Functional assays demonstrated the impact of miR-301a on cell proliferation and apoptosis, particularly in synergy with TNF-α. Overall, our study elucidated the intricate interplay between the Hh and HIPPO/YAP pathways mediated by miR-301a, providing valuable insights into potential therapeutic strategies for intervening in PDAC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2457761"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR4 confers stemness and radioresistance in chordoma cells.","authors":"Chan-Woong Jung, Jeong-Yub Kim, Myung-Jin Park","doi":"10.1080/15384047.2025.2471631","DOIUrl":"10.1080/15384047.2025.2471631","url":null,"abstract":"<p><p>CXC Chemokine receptor type 4 (CXCR4) is commonly considered a potential marker for cancer stem cells (CSCs). Dedifferentiated-type chordoma (DTC) cells derived from a patient with recurrent chordoma exhibit high CXCR4 expression and demonstrate increased resistance to chemotherapeutic drugs and ionizing radiation (IR) compared to the conventional-type chordoma cell line, U-CH1. However, the precise role of CXCR4 in the stemness and IR resistance of DTC remains unclear. Therefore, this study aims to elucidate the correlation between the expression of CXCR4 and stemness and radioresistance in chordoma. DTC cells expressing CXCR4 (CXCR4⁺ DTC cells), isolated by magnetic-activated cell sorting, exhibited increased self-renewal activity, tumorigenicity, and IR resistance, accompanied by elevated Sox2 expression. Knockdown of CXCR4 expression using short hairpin RNA, inhibition of CXCR4 signaling with AMD3100, and targeting of STAT3, a downstream effector of CXCR4, with WP1066 in DTC cells significantly diminished their self-renewal ability, tumorigenic potential, IR resistance, and Sox2 expression. Additionally, transfection with a small interfering Sox2 RNA suppressed self-renewal activity, tumorigenicity, and IR resistance in DTC cells, whereas overexpression of CXCR4 reversed these effects in U-CH1 cells. Furthermore, DTC cells infected with shCXCR4 exhibited substantial tumor suppression, and the combination of IR and AMD3100 significantly reduced DTC tumor growth in a mouse xenograft model. These findings underscore the functional significance of CXCR4 as a CSC marker, highlighting its potential as a therapeutic target for malignant chordomas.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2471631"},"PeriodicalIF":4.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.","authors":"Brajesh P Kaistha, Gozde Kar, Andreas Dannhorn, Amanda Watkins, Grace Opoku-Ansah, Kristina Ilieva, Stefanie Mullins, Judith Anderton, Elena Galvani, Fabien Garcon, Jean-Martin Lapointe, Lee Brown, James Hair, Tim Slidel, Nadia Luheshi, Kelli Ryan, Elizabeth Hardaker, Simon Dovedi, Rakesh Kumar, Robert W Wilkinson, Scott A Hammond, Jim Eyles","doi":"10.1080/15384047.2023.2296048","DOIUrl":"10.1080/15384047.2023.2296048","url":null,"abstract":"<p><p>CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205). This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP). We hypothesize that the improved responses are tumor microenvironment (TME)-driven, as suggested by the lack of anti-CD73 enhanced cytopathic effects mediated by 5FU+OHP on cell lines <i>in vitro</i>. Pharmacodynamic analysis, using imaging mass cytometry and RNA-sequencing, revealed noteworthy changes in specific cell populations like cytotoxic T cells, B cells and NK cells in the CT26 TME. Transcriptomic analysis highlighted treatment-related modulation of gene profiles associated with an immune response, NK and T-cell activation, T cell receptor signaling and interferon (types 1 & 2) pathways. Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2296048"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.","authors":"Kaiwen Zhang, Xingyu Zheng, Yiqing Sun, Xinyu Feng, Xirong Wu, Wenlu Liu, Chao Gao, Ye Yan, Wenyan Tian, Yingmei Wang","doi":"10.1080/15384047.2024.2325126","DOIUrl":"10.1080/15384047.2024.2325126","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2325126"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384047.2024.2375109","DOIUrl":"10.1080/15384047.2024.2375109","url":null,"abstract":"","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2375109"},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}