Anti-Cancer Drugs最新文献

{"title":"Ubiquitination mediated cisplatin resistance in bladder cancer.","authors":"Yuzhong Wang, Junfang Yuan, Shaowei Guo, Yongqiang Liu, Jianguo Ma","doi":"10.1097/CAD.0000000000001816","DOIUrl":"10.1097/CAD.0000000000001816","url":null,"abstract":"<p><p>Bladder cancer (BCa) patients frequently develop resistance to platinum-based therapies, particularly cisplatin. The link between chemoresistance and glycolysis has been well documented. Emerging evidence suggests that Rac family small GTPase 3 ( RAC3 ) may play significant roles in cisplatin resistance. This study investigated the underlying molecular mechanisms. Clinical specimens (cisplatin-sensitive/resistant BCa tissues and matched adjacent normal tissues) were collected from hospital. Cisplatin-resistant cell lines [T24-derived cisplatin-resistant cells (T24-DDP) and 5637-derived cisplatin-resistant cells (5637-DDP)] were generated through stepwise dose escalation. RAC3 , Myc-binding protein 2 (MYCBP2 ), P21-activated kinase 1 ( PAK1 ), Ki-67, and glycolysis markers were analyzed by quantitative PCR, immunohistochemistry, and Western blot. RAC3 ubiquitination was assessed via co-immunoprecipitation. Cell viability, apoptosis, and glycolytic metabolism were evaluated using the cell counting kit-8 assay, terminal deoxynucleotidyl transferase deoxyuridine triphosphate/flow cytometry, and ATP/lactate assays, respectively. Glycolytic flux was measured by extracellular acidification rate. Additionally, BCa xenograft models were established for in-vivo detection. Elevated RAC3 expression and glycolytic activity were observed in BCa tissues, with further augmentation in cisplatin-resistant tumors. RAC3 overexpression promoted cell viability, glycolysis, invasion, and migration in cisplatin-treated T24 and 5637 cells. Conversely, RAC3 knockdown exerted the opposite effects and restored cisplatin sensitivity in resistant T24-DDP and 5637-DDP cells. Notably, the sensitizing effect of RAC3 knockdown was reversed by PAK1 overexpression. Furthermore, MYCBP2 regulated RAC3 stability, as MYCBP2 overexpression enhanced RAC3 ubiquitination, suppressed glycolysis, and sensitized resistant cells to cisplatin. These effects were abrogated by the proteasome inhibitor MG132, confirming proteasome-dependent degradation of RAC3 . MYCBP2 -mediated ubiquitination of RAC3 modulates the PAK1 /pyruvate dehydrogenase E1 subunit alpha axis to regulate glycolytic activity, ultimately determining cisplatin sensitivity in BCa.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"386-400"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728141","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":"Aldehyde dehydrogenase 9A1 promotes cisplatin resistance in laryngeal squamous cell carcinoma by enhancing PTEN-induced kinase 1-Parkin-mediated mitophagy.","authors":"Jiawei Gui, Bo Wu, Yutong Fan, Xiaotong Liu, Yuzhe Liu, Haiying Wang, Jun An, Hao Wang, Ruoqing Wu, Liang Li, Jingchun Ge, Hui Xiao","doi":"10.1097/CAD.0000000000001799","DOIUrl":"10.1097/CAD.0000000000001799","url":null,"abstract":"<p><p>Cisplatin resistance remains a major challenge in laryngeal squamous cell carcinoma (LSCC) treatment. Aldehyde dehydrogenase 9A1 (ALDH9A1), a mitochondrial matrix protein, is dysregulated in various cancers, but its role in LSCC is unclear. This study demonstrates that ALDH9A1 is significantly downregulated in LSCC tissues, and low ALDH9A1 expression correlates with poor patient prognosis. Functionally, ALDH9A1 overexpression inhibits LSCC cell proliferation, migration, and invasion while promoting apoptosis. Mechanistically, ALDH9A1 interacts with and stabilizes PTEN-induced kinase 1 (PINK1), leading to activation of PINK1-Parkin-mediated mitophagy. Under cisplatin treatment, ALDH9A1 is upregulated and induces protective mitophagy, contributing to cisplatin resistance. Inhibition of mitophagy with chloroquine sensitizes LSCC cells to cisplatin. These findings identify ALDH9A1 as a key regulator of mitophagy and cisplatin resistance in LSCC, suggesting that targeting the ALDH9A1/PINK1 axis could provide a novel therapeutic strategy for overcoming cisplatin resistance.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"366-375"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817486","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":"Comparative study of the efficacy and safety of PSOX and SOX plus sintilimab regimens as first-line treatments for advanced gastric cancer.","authors":"Tao Zhang, Wenbin Yang, Chenguang Zhang, Kedi Wang, Hao Li","doi":"10.1097/CAD.0000000000001800","DOIUrl":"10.1097/CAD.0000000000001800","url":null,"abstract":"<p><p>Advanced gastric cancer (AGC) remains associated with poor survival despite advances in multimodal treatment. Recent trials suggest that adding programmed death-1 inhibitors to chemotherapy may improve outcomes in HER2-negative AGC, but real-world evidence-particularly in surgical settings-remains limited. This retrospective study evaluated the efficacy and safety of SOX plus sintilimab compared with P-SOX in patients with AGC undergoing perioperative chemotherapy followed by standard D2 gastrectomy. A total of 242 patients were included, of whom 161 received P-SOX and 81 received SOX plus sintilimab. Short-term response, long-term survival outcomes, and treatment-related adverse events were compared between groups. Prognostic factors for progression-free survival (PFS) were further analyzed in patients treated with SOX plus sintilimab. The SOX plus sintilimab regimen achieved superior short-term efficacy, with higher objective response rates by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (70.4% vs. 47.2%) and higher tumor regression grades (91.4% vs. 72.7%) compared with P-SOX (both P < 0.001). Median overall survival was significantly longer in the SOX plus sintilimab group (32.0 vs. 29.0 months; HR = 0.617, P  = 0.006), while PFS showed a borderline improvement. Treatment-related adverse events were mostly grade 1-2, with comparable rates of severe toxicities between groups; immune-related events were infrequent. Poor perioperative treatment response, larger tumor size, poor differentiation, and advanced stage were independently associated with worse PFS. In conclusion, SOX plus sintilimab offers improved efficacy with acceptable safety compared with P-SOX, providing supportive real-world evidence for its use in AGC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"376-385"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916726","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":"Dual checkpoint inhibition achieves successful treatment of diffuse bilateral lung metastasis in giant advanced liver cancer: a case report.","authors":"Ting-Ting Xie, Wang Chen, Zi-Han Zeng, Ji-Hang Luo, Yan Wang, Xiao-Min Peng, Ming-Dong Lin, Jian Song, Meng Xu, Yin Li","doi":"10.1097/CAD.0000000000001796","DOIUrl":"10.1097/CAD.0000000000001796","url":null,"abstract":"<p><p>Advanced hepatocellular carcinoma (HCC) with extensive metastases is associated with a poor prognosis, highlighting the need for individualized, multimodal treatment strategies. We present the case of a 54-year-old male with advanced HCC (cT3NxM1, Child-Pugh B) and spinal as well as bilateral pulmonary metastases who experienced disease progression after multiple lines of therapy. A dynamically adjusted, multidisciplinary regimen was implemented, incorporating transarterial chemoembolization (TACE), surgery, immunotherapy, and targeted therapy. The final regimen - combining nivolumab plus ipilimumab (O+Y) with TACE and lenvatinib - achieved a partial response in lung metastases, with a progression-free survival exceeding one year and overall survival of over 24 months. This case underscores the therapeutic potential of O+Y in later-line settings and demonstrates the clinical value of an integrated, personalized treatment paradigm for advanced HCC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"401-406"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058890","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":"Fibroblast growth factor receptor 2 mutation-guided targeted therapy with lenvatinib in sebaceous carcinoma of the external auditory canal: a case report and literature review.","authors":"RuGang Zhao, Qing Han, JuYi Wen, XinHong Zhang, Wei Qiu, ShanShan Wu, LiPin Gao, XiangFei Zhao","doi":"10.1097/CAD.0000000000001797","DOIUrl":"10.1097/CAD.0000000000001797","url":null,"abstract":"<p><p>This is the first global report of a successful case of lenvatinib treatment for a rare sebaceous carcinoma originating in the external auditory canal. The patient experienced local recurrence and pulmonary metastasis despite undergoing surgery and radiotherapy. Initial chemotherapy combined with immune checkpoint inhibitors achieved short-term stability, but the disease eventually progressed. Genetic testing revealed an Fibroblast growth factor receptor 2 (FGFR2) mutation, leading to a switch to targeted therapy with lenvatinib combined with capecitabine, demonstrating the value of targeted therapy in the management of rare, refractory sebaceous carcinoma.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"407-409"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931870","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":"Survival advantage of bevacizumab rechallenge in recurrent ovarian cancer regardless of platinum sensitivity.","authors":"Ugur Ozberk, Selin Akturk Esen, Serhat Sekmek, Ismet Seven, Oznur Bal, Efnan Algin, Sebnem Yucel, Dogan Uncu","doi":"10.1097/CAD.0000000000001798","DOIUrl":"10.1097/CAD.0000000000001798","url":null,"abstract":"<p><p>Bevacizumab has demonstrated significant efficacy in both first-line and recurrent settings of epithelial ovarian cancer; however, evidence regarding the benefit of bevacizumab retreatment after prior exposure in real-world populations remains limited. This study aimed to evaluate the efficacy of bevacizumab retreatment compared with nonbevacizumab regimens in recurrent metastatic ovarian carcinoma, irrespective of platinum sensitivity status. This retrospective single-center study included 133 patients with recurrent epithelial ovarian cancer who had previously received bevacizumab-containing first-line therapy between January 2015 and May 2025. Patients were grouped according to second-line treatment: bevacizumab-containing chemotherapy ( n  = 51) or chemotherapy alone ( n  = 82). Patients undergoing secondary cytoreductive surgery were excluded. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression models. Median PFS-2 after second-line treatment was significantly longer in the bevacizumab group compared with the nonbevacizumab group (9.7 vs. 3.0 months; P  < 0.001). This benefit was consistent across both platinum-sensitive and platinum-resistant subgroups. Multivariate analysis confirmed that omission of bevacizumab independently predicted worse PFS-2 (hazard ratio = 3.33, 95% CI: 2.17-5.11, P  < 0.001). Although OS-2 was numerically longer in the bevacizumab group (14.1 vs. 8.2 months), the difference was not statistically significant ( P  = 0.091). Bevacizumab retreatment following prior first-line use was associated with improved PFS regardless of platinum sensitivity, suggesting a potential survival advantage in recurrent ovarian cancer. Prospective, randomized studies including both platinum-sensitive and platinum-resistant patients with larger sample sizes are warranted to confirm these findings and determine the optimal use of bevacizumab beyond first-line therapy.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"359-365"},"PeriodicalIF":2.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808840","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":"Inhibiting FGFR by toadflax reverses erlotinib resistance in nonsmall cell lung cancer.","authors":"Bateer Han, Ying Ma, Shuguang Bao, Hui Gao, Yanqing Gao, Qiang Guo, Ao Li, Meitao Li, Rong Yu, Hongwei Wang","doi":"10.1097/CAD.0000000000001649","DOIUrl":"10.1097/CAD.0000000000001649","url":null,"abstract":"<p><p>This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro , investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo . In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"301-311"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891367","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":"Eugenol as a game-changer: overcoming osimertinib resistance in non-small cell lung cancer by inhibiting glycolysis via the tripartite motif containing 59/extracellular signal-regulated kinase pathway.","authors":"Kun Zhao, Wei Wang, Yansha Sun, Ke Li","doi":"10.1097/CAD.0000000000001793","DOIUrl":"10.1097/CAD.0000000000001793","url":null,"abstract":"<p><p>Eugenol plays a significant role in various cancers and can influence the sensitivity of cancer cells to chemotherapy. This study aimed to investigate the mechanism by which eugenol regulates glycolysis through the tripartite motif containing 59 (TRIM59)/extracellular signal-regulated kinase (ERK) pathway in osimertinib-resistant non-small cell lung cancer (NSCLC). Drug-resistant lung cancer cell lines were established using osimertinib and treated with eugenol at different concentrations for 24 h. After treatment with eugenol, siTRIM59, TRIM59 overexpression, and the ERK inhibitor, either alone or in combination, the cell counting kit-8 was used to assess cell viability in drug-resistant cell lines. Flow cytometry, colony formation assay, and transwell assays were employed to evaluate the effects of eugenol on cell apoptosis, clonogenic ability, migration, and invasion, respectively. Relevant kits were used to measure the glycolytic activity of the cells. Eugenol inhibited the proliferation, invasion, and migration of drug-resistant cells, promoted apoptosis, and reduced glucose consumption, lactate release, and glycolytic activity in drug-resistant cells. TRIM59 expression was higher in drug-resistant cancer cells, while eugenol treatment inhibited the expression of TRIM59 and ERK phosphorylation. Silencing of TRIM59 enhanced the effect of eugenol on drug-resistant cell lines. Overexpression of TRIM59 reversed the effects of eugenol on drug-resistant cell lines, whereas ERK inhibition reversed the effects of TRIM59 and enhanced the therapeutic effects of eugenol on cancer cells. Moreover, eugenol inhibited the tumor growth, TRIM59 expression, and ERK phosphorylation in osimertinib-treated mice. Eugenol can effectively overcome osimertinib resistance in NSCLC by regulating glycolysis through the TRIM59/ERK signaling pathway. Eugenol could serve as a promising adjunctive therapy to improve chemotherapy efficacy and overcome drug resistance in NSCLC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"312-328"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720537","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":"Hematopoietic progenitor kinase 1 inhibitor BGB-15025 induces apoptosis in acute myeloid leukemia cells through the cell cycle pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway signaling axis.","authors":"Shiyu Yang, Fenglin Li, Haihui Zhuang, Dong Chen, Xia Jiang, Yanhan Zhou, Renzhi Pei, Shuangyue Li, Peipei Ye, Ying Lu","doi":"10.1097/CAD.0000000000001794","DOIUrl":"10.1097/CAD.0000000000001794","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy originating from the malignant clonal proliferation of hematopoietic stem/progenitor cells and is associated with a poor prognosis. Hematopoietic progenitor kinase 1 (HPK1, MAP4K1), a member of the MAP4K family, plays a critical role in immunomodulation and oncogenesis. Previous studies have highlighted its pro-oncogenic function in AML, suggesting its potential as both a prognostic marker and therapeutic target. This study aimed to investigate the anti-AML effects of the novel HPK1 inhibitor BGB-15025. We utilized preclinical models, including AML cell lines, primary patient-derived cells, and MV4-11 xenograft mice. Mechanistic investigations were conducted using RNA sequencing and Western blot analysis. BGB-15025 exerted potent cytotoxicity against AML cells and primary progenitors, inducing apoptosis and G0/G1 cell cycle arrest via downregulation of cyclin D1-cyclin-dependent kinase 4 and upregulation of P21. The inhibitor suppressed mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling through reduced phosphorylation of P38 and ERK. In-vivo studies demonstrated a reduced leukemia burden in xenograft models. This study is the first to elucidate that BGB-15025 triggers AML apoptosis through cell cycle blockade and MAPK pathway inhibition, thereby proposing a novel precision therapeutic strategy with significant clinical translational value.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"329-342"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916651","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":"Treatment of HRD-positive elderly ovarian cancer patient: a case report.","authors":"Yuxin Jiang, Qijun Yi, Yueer Wang, Chen Li, Haiyan Liu","doi":"10.1097/CAD.0000000000001772","DOIUrl":"10.1097/CAD.0000000000001772","url":null,"abstract":"<p><p>The standard treatment for advanced ovarian cancer follows a comprehensive 'surgery-chemotherapy-maintenance therapy' mode, typically involving initial cytoreductive surgery aiming for R0 resection, six cycles of platinum-based chemotherapy, followed by maintenance therapy for those who have responded well to the treatment. However, frailty and high incidence of comorbidities in elderly patients often compromise surgical outcomes, necessitate chemotherapy dose reductions, and limit maintenance therapy continuation, resulting in a poor prognosis. Poly (Adenosine diphosphate (ADP)-ribose) polymerase inhibitors (PARPi) have revolutionized the management strategy of homologous recombination deficiency (HRD)-positive patients as a groundbreaking advancement in first-line maintenance therapy. Fluzoparib, the domestically developed PARPi in China, has demonstrated significant efficacy in BRCA-mutated ovarian cancer. In the field of supportive care, megestrol acetate (MA) is recommended as the first-line preferred therapeutic agent for cancer-related anorexia by major guidelines, though its role in first-line ovarian cancer therapy remains unexplored, and evidence for its combination with PARPi is lacking. This article reported a case of an 89-year-old female patient with high-grade serous ovarian carcinoma. Due to intolerance to surgery and chemotherapy, an innovative first-line primary treatment regimen combining fluzoparib with MA was initiated based on BRCA2 mutation and HRD-positive status. Imaging assessments revealed significant tumor reduction without disease progression or grade ≥3 adverse events observed throughout follow-up. This case highlights the potential of combining PARPi and hormone therapy as a 'chemotherapy-free' precision treatment model for elderly and HRD-positive ovarian cancer patients, offering a promising strategy to balance efficacy and tolerability in a population traditionally underserved by conventional regimens.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":"352-357"},"PeriodicalIF":2.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627982","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}