Therapeutic Advances in Medical Oncology最新文献

{"title":"Tumor distribution type helps distinguish the prognosis of HCC patients with multiple tumors in BCLC-A stage: a multi-center retrospective study.","authors":"WenZhen Ding, Xueqin Tian, Yongfeng Yang, Haokai Xu, Xin Li, Jie Yu, Ping Liang","doi":"10.1177/17588359251403407","DOIUrl":"10.1177/17588359251403407","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) patients with multiple tumors have a poor prognosis and need more attention.</p><p><strong>Objectives: </strong>To develop an easily available radiological indicator that can differentiate the prognosis of Barcelona Clinic Liver Cancer stage A (BCLC-A) patients with multiple tumors.</p><p><strong>Design: </strong>This was a retrospective, multicenter study. Magnetic resonance imaging (MRI) data were collected from patients who underwent thermal ablation (TA), laparoscopic hepatectomy (LH), or LH combined with TA at five tertiary hospitals.</p><p><strong>Methods: </strong>Tumor distribution (TD) was classified into three types: same-segment, different-segments, and different-lobes, and three junior doctors (<5 years of experience) were invited to classify the tumors. We compared disease-free survival (DFS) and overall survival (OS) among the different TD types and performed pathological consistency and classification analyses. Six pathological indicators (tumor differentiation, alpha-fetoprotein (AFP), arginase-1 (Arg-1), hepatocyte paraffin 1, cytokeratin-19 (CK-19), and vascular endothelial growth factor (VEGF)) were included.</p><p><strong>Results: </strong>A total of 373 patients were included with a 36.0-month median follow-up. The Fleiss kappa score among the three doctors was 0.803. Patients with the same-segment type had better DFS and OS than those with different-segment (<i>p</i> < 0.001) and different-lobe (<i>p</i> < 0.001) types; therefore, the same segment was defined as a concentrated distribution. Different segments and lobes had comparable DFS (<i>p</i> = 0.072) and OS (<i>p</i> = 0.830) and were defined as having dispersed distributions. Patients in concentrated group had higher pathological consistency in tumor-differentiation (96.2% vs 86.7%, <i>p</i> = 0.003), AFP (95.3% vs 84.4%, <i>p</i> = 0.005), Arg-1 (96.7% vs 83.3%, <i>p</i> = 0.001) and CK-19 (96.0% vs 82.4%, <i>p</i> = 0.004), and better tumor-differentiation (23.3% vs 41.7%, <i>p</i> < 0.001) and lower expression rate in AFP (36.8% vs 49.5%, <i>p</i> = 0.035), CK-19 (9.3% vs 24.3%, <i>p</i> = 0.008), and VEGF (17.0% vs 39.3%, <i>p</i> = 0.004) than dispersed group.</p><p><strong>Conclusion: </strong>We established a method based on MRI to accurately differentiate the TD type of multiple tumors for patients in the BCLC-A stage. Patients with concentrated distribution tumors had a better prognosis than patients with dispersed distribution.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251403407"},"PeriodicalIF":4.2,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12718338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145811071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current landscape of sequencing ADCs in metastatic breast cancer.","authors":"Shannon McLaughlin, Lis V Ravani, Beverly Moy, Arielle J Medford, Steven J Isakoff, Ting Liu, Leif W Ellisen, Laura M Spring, Seth A Wander, Rachel O Abelman","doi":"10.1177/17588359251396656","DOIUrl":"10.1177/17588359251396656","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have revolutionized the care of advanced breast cancer. ADCs pair an antibody targeted against a tumor-associated antigen with a cytotoxic payload, aiming to deliver therapy more effectively and with fewer off-target toxicities. Given the growth of ADCs in the past few years, patients are now candidates for multiple agents sequentially. Optimal strategies for sequencing ADCs are not yet known. Here we review retrospective data on ADC sequencing, translational understanding of mechanisms of resistance, and novel ADCs and combination agents in the pipeline that aim to improve upon currently available care.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251396656"},"PeriodicalIF":4.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic role of the neutrophil-to-lymphocyte ratio in metastatic urothelial carcinoma.","authors":"Sevinc Balli, Fatih Yildiz, Mehmet Ali Nahid Sendur, Nuriye Yildirim Ozdemir, Oguzcan Gumuscubuk, Emre Yekeduz, Yuksel Urun","doi":"10.1177/17588359251403390","DOIUrl":"10.1177/17588359251403390","url":null,"abstract":"<p><strong>Background: </strong>Systemic inflammation has been linked to cancer progression and survival outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a readily available biomarker that may reflect this process in metastatic urothelial carcinoma (mUC).</p><p><strong>Objectives: </strong>To evaluate the prognostic impact of baseline NLR on overall survival in mUC patients receiving chemotherapy or immunotherapy.</p><p><strong>Design: </strong>A multicenter retrospective cohort study.</p><p><strong>Methods: </strong>We retrospectively analyzed 196 patients with advanced, unresectable urothelial carcinoma treated at four centers (Ankara University School of Medicine, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara Bilkent City Hospital, and Gazi University School of Medicine) between 2005 and 2023. These patients were stratified into high and low NLR groups using a cutoff of 4.2. Survival outcomes were assessed using Kaplan-Meier curves, and the prognostic significance of NLR was evaluated using univariate (log-rank test) and multivariate (Cox proportional hazards model) analyses.</p><p><strong>Results: </strong>The median overall survival (OS) for the entire cohort was 27 months (95% CI: 19.1-34.9). Patients with low NLR had significantly longer OS than those with high NLR (56.6 vs 14.6 months; <i>p</i> < 0.001). In multivariate analysis, NLR remained an independent predictor of OS after adjusting for age, liver metastases, and bone metastases (HR: 2.28, 95% CI: 1.37-3.81; <i>p</i> = 0.002).</p><p><strong>Conclusion: </strong>Elevated NLR is an independent prognostic marker in mUC, underscoring the role of systemic inflammation in cancer progression. These findings highlight the potential of NLR as a readily available biomarker for risk stratification in mUC, irrespective of treatment modality.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251403390"},"PeriodicalIF":4.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-drug conjugates outperform chemotherapy in EGFR-TKI-resistant NSCLC: a Bayesian network meta-analysis.","authors":"Yueying Chen, Yanjun Du, Juan Ni, Dong Wang, Ping Zhan, Yong Song, Hedong Han, Tangfeng Lv","doi":"10.1177/17588359251405044","DOIUrl":"10.1177/17588359251405044","url":null,"abstract":"<p><strong>Background: </strong>While developments in targeted therapy have marked a new epoch for non-small cell lung cancer (NSCLC) patients harboring actionable genomic alterations, the management of individuals resistant to epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) remains a formidable challenge.</p><p><strong>Objectives: </strong>This study was designed to evaluate the comparative efficacy and safety of available therapeutic regimens and to identify the optimal treatment strategy for patients with disease progression following EGFR-TKI therapy.</p><p><strong>Design: </strong>This is a systematic review and Bayesian network meta-analysis.</p><p><strong>Data sources and methods: </strong>Databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov, along with conference proceedings from January 1, 2020, to June 1, 2025, were searched. Randomized controlled trials (RCTs) assessing treatment options for advanced NSCLC patients resistant to EGFR-TKIs were eligible. We identified the optimal therapeutics through comparison of the surface under the cumulative ranking curves (SUCRA).</p><p><strong>Results: </strong>Overall, 19 RCTs involving 4,039 participants were identified. Meta-analysis indicated that sacituzumab tirumotecan (Sac-TMT) significantly improved progression-free survival (PFS; hazard ratio [HR] 0.20, 95% credible interval [CI] 0.13-0.30) and overall survival (OS; HR 0.36, 95% CI 0.20-0.66) compared to conventional chemotherapy as evidenced by its superior SUCRA values (0.997 for PFS and 0.946 for OS). Datopotamab deruxtecan (Dato-DXd) also demonstrated clinically meaningful efficacy outcomes. Specifically, Sac-TMT showed statistically superior PFS benefits relative to nearly all comparator regimens, including immune checkpoint inhibitor (ICI)-based and bispecific antibody (bsAb)-based strategies (all <i>p</i> < 0.05). Amivantamab in combination with lazertinib and chemotherapy (SUCRA = 0.816) and ivonescimab combined with chemotherapy (SUCRA = 0.779) both exhibited capabilities in prolonging PFS. Notably, the triplet regimen was associated with the highest incidence of severe-grade AEs compared to all other treatment options.</p><p><strong>Conclusion: </strong>Sac-TMT, Dato-DXd, and bsAbs-based regimens were identified as the most efficacious options with manageable toxicity for advanced NSCLC patients who progressed after EGFR-TKIs. These findings underscore the pivotal role of innovative therapeutic agents, illuminating potential treatment avenues for this difficult-to-treat refractory population.</p><p><strong>Trial registration: </strong>This study was registered as INPLASY202510014.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251405044"},"PeriodicalIF":4.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of immunotherapy efficacy for pulmonary lymphoepithelioma-like carcinoma using baseline routine blood tests and serum tumor markers: a multicenter retrospective study.","authors":"Xiongwen Yang, Yuanwei Liang, Hao Hu, Yubin Zhou, Huiyin Deng, Jian Huang, Maoli Liang, Zihao Yuan, Longyan Dong, Yi Xiao","doi":"10.1177/17588359251403409","DOIUrl":"10.1177/17588359251403409","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare Epstein-Barr virus-associated subtype of non-small cell lung cancer. Although immune checkpoint inhibitors (ICIs) have shown promising activity, robust predictors of benefit remain lacking. Programmed death-ligand 1 (PD-L1) is widely used but has limited accuracy. Routine blood tests and serum tumor markers (STMs) are inexpensive and universally available, yet their prognostic value in pLELC has not been systematically evaluated.</p><p><strong>Objectives: </strong>To develop and validate a composite blood-based score integrating hematologic indices and STMs for predicting immunotherapy outcomes in advanced pLELC.</p><p><strong>Design: </strong>Multicenter retrospective cohort study.</p><p><strong>Methods: </strong>We retrospectively analyzed 254 patients with advanced pLELC treated with ICIs across six tertiary centers in China. Baseline hematologic indices, serum biochemistry, and STMs were collected. A composite Blood Routine & Tumor-Marker Score (BRTS) was constructed using LASSO Cox regression with progression-free survival (PFS) as the endpoint. Patients were stratified into high- and low-BRTS groups, and prognostic value was validated in an independent cohort. Nomograms combining BRTS with clinical variables were developed and internally validated.</p><p><strong>Results: </strong>High BRTS was associated with significantly shorter PFS and overall survival (OS) in both training (hazard ratio (HR) for PFS = 4.59; OS = 6.86) and validation cohorts (HR for PFS = 5.37; OS = 3.87; all <i>p</i> < 0.001). In multivariate analyses, BRTS remained an independent predictor alongside treatment line, regimen, and liver metastasis, whereas PD-L1 expression lost significance. Nomograms incorporating BRTS demonstrated good discrimination (C-index ~0.79), calibration, and clinical net benefit. Prognostic utility was consistent across treatment lines.</p><p><strong>Conclusion: </strong>The BRTS, derived from widely available laboratory tests, robustly stratified immunotherapy outcomes in advanced pLELC and outperformed PD-L1 alone. This simple, low-cost tool may facilitate individualized treatment decisions and warrants prospective validation.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251403409"},"PeriodicalIF":4.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145782927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-agnostic therapy: a potential therapeutic approach for SMARCA4-deficient malignancies.","authors":"Yang Liu, Zhi-Hui Liu, Qiong Zhang, Yin-Miao Bai, Xiao-Bo Guo, Hong-Chen Ji, Hong-Mei Zhang","doi":"10.1177/17588359251399031","DOIUrl":"10.1177/17588359251399031","url":null,"abstract":"<p><p>SMARCA4 deficiency plays a critical role in the oncogenesis of various aggressive tumors that exhibit resistance to conventional chemotherapy and radiotherapy, posing significant challenges to clinical management. The pivotal role of SMARCA4 deficiency in tumorigenesis suggests the need for a paradigm shift from traditional tumor origin-based approaches to novel tumor-agnostic strategies focused on molecular alterations associated with SMARCA4 deficiency. This review explores potential targetable molecular changes and emerging therapeutic strategies for SMARCA4-deficient tumors. Molecular alterations related to SMARCA4 deficiency involve impaired genomic stability, defects in DNA mismatch repair, and elevated tumor mutation burdens, all of which suggest potential sensitivity to immune checkpoint inhibitors (ICIs). Recent studies indicate that combining ICIs with chemotherapy or anti-angiogenic agents as first-line treatments may offer clinical benefits for SMARCA4-deficient tumors. Furthermore, SMARCA4 deficiency epigenetically affects chromatin accessibility, alters the distribution of Polycomb group proteins on chromatin, and modulates histone acetylation, highlighting the potential efficacy of epigenetic regulators such as EZH2 and HDAC inhibitors. In addition, synthetic lethality strategies targeting vulnerabilities in SMARCA4-deficient tumors are promising therapeutic approaches, including inhibitors of SMARCA2, CDK4/6, ATR, CHK1, PARP, and the oxidative phosphorylation pathway. Based on current clinical evidence, ICI-based combination therapies represent the most promising first-line regimens for SMARCA4-deficient tumors. Although a theoretical basis supports the potential of tumor-agnostic therapy as a promising strategy for these tumors, several challenges remain in clinical practice. These include heterogeneous therapeutic responses across tumor types, safety concerns associated with synthetic lethality-based agents, and the absence of any histology-agnostic approved therapy for SMARCA4-deficient tumors. The continued development of novel therapeutics and further large-scale clinical evaluations are essential to overcoming these barriers.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251399031"},"PeriodicalIF":4.2,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic and locoregional therapies for cutaneous metastases from breast cancer: state of art and new frontiers in treatment approach.","authors":"Francesco Russano, Davide Brugnolo, Michele Bottosso, Luigi Dall'Olmo, Paolo Del Fiore, Rino Baldan, Massimo Ferrucci, Noemi Musilli, Maria Vittoria Dieci, Valentina Guarneri, Marco Rastrelli, Simone Mocellin","doi":"10.1177/17588359251387539","DOIUrl":"10.1177/17588359251387539","url":null,"abstract":"<p><p>Cutaneous metastases from breast cancer, although relatively uncommon, represent the most frequent form of skin metastases overall and pose a significant clinical and therapeutic challenge. Their presence classifies the disease as stage IV, typically prompting the initiation or modification of systemic treatment. However, current clinical guidelines do not distinguish between cutaneous and visceral metastases, which may lead to unnecessary alterations in systemic therapy-even when visceral disease remains well controlled-potentially compromising an otherwise effective regimen. This review provides a comprehensive overview of systemic and loco-regional treatment options for cutaneous breast cancer metastases, including current guidelines stratified by tumor subtype. Special attention is given to loco-regional therapies such as electrochemotherapy, radiotherapy, surgical excision, photodynamic therapy, intralesional agents, and topical treatments, all of which can be integrated with systemic therapy to improve local disease control, reduce symptoms, and enhance patient quality of life. We propose an integrated and personalized therapeutic model that combines systemic and loco-regional approaches, supported by a decision-making flowchart designed to assist clinicians in optimizing treatment strategies. By adopting a multidisciplinary perspective, this approach aims to improve both local and systemic disease management, clinical outcomes, and patient well-being. Further research is warranted to refine therapeutic combinations, establish standardized protocols, and fully realize the clinical benefits for patients with metastatic breast cancer presenting with cutaneous involvement.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251387539"},"PeriodicalIF":4.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting synthetic lethality: an effective therapeutic approach in ovarian and endometrial cancers.","authors":"Alizée Lebeau, Athanasios Kakkos, Natacha Leroi, Vincent Bours, Katty Delbecque, Frédéric Goffin, Elodie Gonne, Christine Gennigens","doi":"10.1177/17588359251392106","DOIUrl":"10.1177/17588359251392106","url":null,"abstract":"<p><p>Synthetic lethality (SL) is a promising therapeutic concept that relies on the indirect targeting of vulnerabilities acquired through genetic mutations. Ovarian and endometrial cancers frequently exhibit mutations in the breast cancer (BRCA), phosphatase and tensin homolog (PTEN), AT-rich interactive domain-containing protein 1A (ARID1A) and TP53 genes, as well as DNA repair pathway deficiencies. Poly(ADP-ribose) polymerase inhibitors (PARPis) have demonstrated remarkable efficacy in various cancers with BRCA mutations and homologous recombination deficiency. In addition to PARPi, there has been an expansion of drugs exploiting the selective vulnerability of cancer cells via SL, such as WEE1 kinase and Ataxia Telangiectasia and Rad3-related protein (ATR). WEE1 inhibitors have shown encouraging results in combination with chemotherapy, increasing the objective response rate in patients with platinum-resistant TP53-mutated ovarian cancer. ATR inhibitors are currently being evaluated in ARID1A-mutated tumours, with preliminary results confirming their therapeutic potential.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251392106"},"PeriodicalIF":4.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics of ovarian cancers and the potential of precision medicine.","authors":"Andrew Jarratt, Joseph Polidano, Clare L Scott, Holly E Barker","doi":"10.1177/17588359251396651","DOIUrl":"10.1177/17588359251396651","url":null,"abstract":"<p><p>Epithelial ovarian cancer (OC) comprises molecularly distinct disease types, with high-grade serous ovarian cancer (HGSOC) accounting for ~75% of OC diagnoses; ovarian clear cell carcinoma (OCCC) and endometrioid ovarian carcinoma (EnOC) at ~10% each; mucinous ovarian carcinoma (MOC) and low-grade serous ovarian carcinoma (LGSOC) at ⩽5% each; and ovarian carcinosarcoma (OCS), the rarest type of OC at 1%-4% of OC diagnoses. LGSOC has the best prognosis, followed by EnOC, MOC and OCCC, with HGSOC then OCS being the most aggressive. For all types of OC, diagnosis at the advanced-stage results in dramatically reduced survival. Initial treatment consists of debulking surgery and platinum-based chemotherapy, usually in combination with a taxane; however, response rates vary depending on the OC type. Treatments specific to the OC type may improve treatment outcomes. For HGSOC, poly(ADP-ribose) polymerase inhibitor (PARPi) therapy has improved survival for women with DNA homologous recombination repair (HRR) defects; however, acquired resistance remains an issue and more effective treatments are needed. Next-generation sequencing of distinct types of OC has revealed the complexity of genetic variants and larger-scale genomic and epigenomic alterations harboured, including proven and putative biomarkers of drug response. A predominance of distinct gene classes is altered in specific OC types: HRR genes (e.g. <i>BRCA1</i> and <i>BRCA2</i>) in HGSOC; <i>ARID1A</i> and <i>PIK3CA</i> in OCCC; <i>PIK3CA</i> and <i>KRAS</i> in EnOC; <i>CDKN2A</i> and <i>KRAS</i> in MOC and MAPK pathway genes (e.g. <i>BRAF</i> and <i>KRAS</i>) in LGSOC. Generating evidence for effective drug combination therapies targeting relevant aberrations in each OC type is urgently needed. The effects of long-term drug treatment on OC genomes, acquired drug-resistance and OC relapse require clarification, especially in women with HGSOC with acquired resistance to PARPi. This article provides an overview of the main types of OC and their genomic profiles. It highlights recent encouraging clinical trials, with an emphasis on the future of genomically-targeted combination therapies, for both first-line and subsequent treatment of OC. We focus on PARPi combinations for HGSOC, MAPK pathway inhibitors for LGSOC, cell cycle checkpoint inhibitors for OC with <i>CCNE1</i> amplification, the potential of immune checkpoint inhibitors in OCCC and encouraging, as yet preliminary, responses for antibody-drug conjugate-based therapy. Thus, OC type-specific genomic susceptibilities provide direction for personalised therapy in OC.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251396651"},"PeriodicalIF":4.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12682999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of neoadjuvant immunochemotherapy in non-small-cell lung cancer: a comparative study of patients above and below 70 years.","authors":"Yuting Zheng, Mengting Huang, Qinyue Luo, Yimeng He, Hanting Li, Xiaoyu Han, Lijie Zhang, Heshui Shi","doi":"10.1177/17588359251399035","DOIUrl":"10.1177/17588359251399035","url":null,"abstract":"<p><strong>Background: </strong>The aging population presents significant challenges to healthcare worldwide. Evidence concerning the safety and efficacy of neoadjuvant immunochemotherapy in patients with non-small-cell lung cancer (NSCLC) aged 70 years or older remains limited.</p><p><strong>Objectives: </strong>To investigate the safety and efficacy of neoadjuvant immunochemotherapy in NSCLC patients stratified by age into three groups, and to identify factors associated with overall survival (OS) and disease-free survival (DFS).</p><p><strong>Design: </strong>We performed a retrospective cohort study including 171 NSCLC patients with NSCLC who underwent neoadjuvant immunochemotherapy followed by surgical resection. The patients were categorized by age into three groups: ⩾70 years, 60-69 years, and <60 years.</p><p><strong>Methods: </strong>The safety and efficacy of neoadjuvant immunochemotherapy were comprehensively evaluated. Safety was assessed based on the incidence of treatment-related adverse events (AEs) and complications. Efficacy was determined through analyses of tumor response and survival outcomes. OS and DFS were analyzed using the Kaplan-Meier method, and independent prognostic factors were identified through the Cox proportional hazards model.</p><p><strong>Results: </strong>The study cohort comprised 24 patients aged ⩾70 years, 73 patients aged 60-69 years, and 74 patients under 60 years. OS and DFS did not differ significantly among the three age groups following neoadjuvant immunochemotherapy. Multivariate analysis identified major pathological response (MPR) as a significant independent predictor of OS (hazard ratio (HR): 0.232, 95% confidence interval (CI): 0.079-0.678, <i>p</i> = 0.008). For DFS, both MPR (HR: 0.342, 95% CI: 0.184-0.638, <i>p</i> = 0.001) and the occurrence of postoperative complications (HR: 2.115, 95% CI: 1.208-3.705, <i>p</i> = 0.009) were independent predictors. Overall, patients across all age groups exhibited acceptable tolerance to neoadjuvant immunochemotherapy.</p><p><strong>Conclusion: </strong>Neoadjuvant immunochemotherapy demonstrated consistent safety and efficacy across all age groups in this cohort of NSCLC patients. Achieving MPR was associated with improved OS and DFS, whereas the occurrence of postoperative complications was associated with diminished DFS.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"17 ","pages":"17588359251399035"},"PeriodicalIF":4.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12681580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145709297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}