Therapeutic Advances in Medical Oncology最新文献

{"title":"NALIRIFOX versus liposomal irinotecan plus fluorouracil/leucovorin as the second-line chemotherapy in gemcitabine refractory pancreatic adenocarcinoma: a real-world study.","authors":"Wei-Ze Wong, Nai-Jung Chiang, Kuei-Chuan Lee, Hung-Yuan Yu, Chia-Jui Tsai, Shao-Jung Hsu, Pei-Chang Lee, Ming-Huang Chen, Hui-Chun Huang, Chung-Pin Li, Jiing-Chyuan Luo, Fah-Yauh Lee","doi":"10.1177/17588359261431386","DOIUrl":"10.1177/17588359261431386","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma has a high mortality rate. Nanoliposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI/FL) is the standard second-line chemotherapy after gemcitabine-based therapy. Although nanoliposomal irinotecan plus oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) has shown superior efficacy as first-line therapy over gemcitabine and nab-paclitaxel, its roles as second-line therapy remains undefined.</p><p><strong>Objectives: </strong>We aimed to compare the clinical outcomes and safety profiles of NALIRIFOX and nal-IRI/FL when used as a second-line treatment for patients with pancreatic adenocarcinoma who have progressed on a gemcitabine-based therapy.</p><p><strong>Designs: </strong>This was a single-center retrospective cohort study.</p><p><strong>Methods: </strong>We included patients with locally advanced or metastatic pancreatic adenocarcinoma who received NALIRIFOX or nal-IRI/FL following progression on first-line gemcitabine-based therapy from September 2020 to October 2024.</p><p><strong>Results: </strong>A total of 62 patients in the NALIRIFOX group and 131 in the nal-IRI/FL group were analyzed. Cumulative dose intensity ⩾80% over four cycles was achieved in 81.4% of the NALIRIFOX group and 73.1% of the nal-IRI/FL group (<i>p</i> = 0.32). The median progression-free survival (PFS) was 4.0 months (95% confidence interval (CI): 3.6-4.5) in the NALIRIFOX group versus 2.5 months (95% CI: 2.1-3.0) in the nal-IRI/FL group (hazard ratio (HR): 0.686; 95% CI: 0.497-0.947; <i>p</i> = 0.021), and the median overall survival was 7.0 months (95% CI: 5.0-9.1) versus 6.3 months (95% CI: 4.4-8.1), respectively (<i>p</i> = 0.827). Of the patients with disease progression after nal-IRI/FL, 69.1% received oxaliplatin-containing chemotherapy. Grade 3-4 adverse events were more frequent with NALIRIFOX, including febrile neutropenia, neutropenia, thrombocytopenia, and peripheral neuropathy; however, most were transient and manageable.</p><p><strong>Conclusion: </strong>NALIRIFOX provides superior PFS compared to nal-IRI/FL as second-line therapy for advanced or metastatic pancreatic cancer after gemcitabine failure. Although NALIRIFOX was associated with higher rates of hematologic and neurologic toxicities, they were manageable with careful monitoring.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261431386"},"PeriodicalIF":4.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514814","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":"Perineural invasion and risk of lymph node metastasis in early-stage operable breast cancer: a large-scale propensity-matched cohort study and meta-analysis.","authors":"Weifeng Cai, Yali Wang, Yibin Qiu, Peng He, Qindong Cai, Shunyi Liu, Jiaqi Zhan, Minyan Chen, Lili Chen, Chunsen Xu, Shunguo Lin, Fangmeng Fu, Chuan Wang","doi":"10.1177/17588359261424685","DOIUrl":"10.1177/17588359261424685","url":null,"abstract":"<p><strong>Background: </strong>Perineural invasion (PNI) is recognized as a prognostic factor in several cancers, but its role in predicting axillary lymph node metastasis (ALNM) in early-stage breast cancer remains unclear. Understanding this association could provide insights for nodal staging in the era of axillary surgery de-escalation, guiding adjuvant treatment decisions.</p><p><strong>Objectives: </strong>To investigate and validate the association between PNI and both the presence and extent of ALNM in patients with early-stage operable invasive breast cancer.</p><p><strong>Design: </strong>A retrospective cohort study and meta-analysis.</p><p><strong>Methods: </strong>We conducted a retrospective study of patients with early-stage operable breast cancer who underwent surgery between June 2011 and June 2023 stratified by PNI status. Three matching methods-propensity score matching, inverse probability of treatment weighting, and overlap weighting-were used to minimize confounding. Multivariable logistic regression analysis was used to assess the association between PNI and both ALNM and lymph node ratio (LNR). In addition, a meta-analysis was conducted to verify these associations.</p><p><strong>Results: </strong>Among 4156 patients, 1223 (29.4%) were PNI-positive. PNI-positive patients had a significantly higher incidence of ALNM (54.0% vs 32.1%) and increased lymph node burden (LNR >0.20). These associations remained significant after adjusting for confounding variables and through sensitivity analyses using the three matching methods (all <i>p</i> < 0.05). In the meta-analysis, 16 cohort studies comprising 17,451 participants met the selection criteria. The analysis confirmed a significant association between PNI and increased ALNM risk (odds ratio (OR), 3.30; 95% confidence interval (CI), 2.24-4.86), poorer disease-free survival (hazard ratio (HR), 1.84; 95% CI, 1.39-2.44), and poorer overall survival (HR, 1.64; 95% CI, 1.15-2.35).</p><p><strong>Conclusion: </strong>PNI is significantly associated with increased ALNM and lymph node burden in early-stage operable breast cancer. These findings support the clinical utility of PNI for risk stratification and as a potential indicator for guiding adjuvant treatment decisions.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261424685"},"PeriodicalIF":4.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514959","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":"Ablation of pulmonary oligometastasis in advanced hepatocellular carcinoma treated with Lenvatinib: a retrospective multicenter study.","authors":"Ye Li, Yigong Ren, Hui Li, Ruixia Li, Hongji You, Yanyang Zhang, Wei Wang, Mingyu Liu, Zhimei Huang, Qunfang Zhou, Feng Duan","doi":"10.1177/17588359261432042","DOIUrl":"10.1177/17588359261432042","url":null,"abstract":"<p><strong>Background: </strong>In patients with hepatocellular carcinoma (HCC) and pulmonary oligometastasis (PO), the therapeutic effects of metastases ablation remain unclear.</p><p><strong>Objective: </strong>This study aimed to compare the efficacy of metastases ablation combined with Lenvatinib (Ablation + Len) with that of Lenvatinib alone (Len) in patients with HCC and PO.</p><p><strong>Design: </strong>A multicenter retrospective study.</p><p><strong>Methods: </strong>This study included 202 patients in the Len group and 182 patients in the Ablation + Len group. Propensity score matching and inverse probability treatment weighting analyses were used to balance baseline variables between the two groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoint was overall survival (OS).</p><p><strong>Results: </strong>The median PFS time was 11.0 ± 0.3 and 14.1 ± 0.5 months in the Len and Ablation + Len groups, respectively. The PFS (hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.49-0.80, <i>p</i> < 0.001) and OS (HR, 0.60; 95% CI, 0.42-0.86; <i>p</i> = 0.006) times were significantly longer in the Ablation + Len group than in the Len group. The OS (HR, 0.62; 95% CI, 0.37-1.03; <i>p</i> = 0.071) and PFS (HR, 0.77; 95% CI, 0.51-1.17; <i>p</i> = 0.230) did not differ among patients with hepatic tumors in stable disease (SD) status. However, among patients in partial response, the OS (HR, 0.57; 95% CI, 0.34-0.95; <i>p</i> = 0.030) and PFS (HR, 0.50; 95% CI, 0.37-0.69; <i>p</i> < 0.001) were significantly different between the two groups.</p><p><strong>Conclusion: </strong>Ablation of PO combined with Lenvatinib resulted in longer PFS and OS than treatment with Lenvatinib alone. However, patients did not derive survival benefits from the ablation of metastases when the hepatic tumors were in SD status.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261432042"},"PeriodicalIF":4.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514314","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":"Molecular complete response to the RIN protocol (regorafenib, ipilimumab, and nivolumab) in a patient with advanced recurrent metastatic mismatch repair proficient/microsatellite stable (pMMR/MSS) rectal cancer.","authors":"Fatima Qadri, Maaz Khan Afghan, Areeb Lutfi, Sana Javaid, Preethi Guniganti, Higinia Cardenes, Alessio Pigazzi, Pashtoon Murtaza Kasi","doi":"10.1177/17588359261432049","DOIUrl":"10.1177/17588359261432049","url":null,"abstract":"<p><p>Rectal cancer recurrence remains a major therapeutic challenge, particularly in patients unresponsive to conventional regimens. Tumors with mismatch-repair-proficient (pMMR) or microsatellite-stable (MSS) status represent the majority of colorectal cancers and are characteristically resistant to immune checkpoint inhibitors. We report a 50-year-old woman with recurrent metastatic KRAS-G12D mutant MSS rectal adenocarcinoma refractory to and with complications to standard chemotherapy regimens who achieved a complete and durable molecular response following initiation of the RIN protocol, a combination of regorafenib, ipilimumab, and nivolumab. A sustained decline in biomarker levels was observed, with both circulating tumor DNA and carcinoembryonic antigen becoming undetectable within 6 months, consistent with a complete molecular response accompanied by a marked interval decrease in FDG-avid disease and sustained radiologic and pathologic remission. This case illustrates the potential for multimodal immune modulation to overcome intrinsic resistance in pMMR/MSS in non-liver metastatic (NLM) colorectal cancer. While previous studies have demonstrated limited benefit of immunotherapy in this tumor subtype, the present findings suggest an emerging therapeutic opportunity that warrants prospective evaluation to confirm efficacy, explore the mechanistic basis, and identify biomarkers predictive of durable response beyond the absence of liver metastases. More effective combinatorial regimens like zanzalintinib and atezolizumb (STELLAR-303) trial, as well as newer generation of CTLA-4 inhibitors like botensilimab, vilastobart, and muzastotug are showing more promise for patients with MSS colorectal cancers in particular who do not have liver metastases (NLM).</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261432049"},"PeriodicalIF":4.2,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514821","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":"Detection of actionable mutations in the cerebrospinal fluid and concordance/discordance with extracranial mutations in patients with metastatic breast cancer and leptomeningeal disease.","authors":"Laura A Huppert, Samantha Fisch, Lindy Her, Christine Hodgdon, Susie Brain, Carol Simmons, Andrew R Lai, Lev Malevanchik, Ronald Balassanian, Harish N Vasudevan, Ramin Morshed, Steve Braunstein, Lauren Boreta, Melanie Majure, A Jo Chien, Hope S Rugo, Mark Jesus M Magbanua, Michelle E Melisko","doi":"10.1177/17588359261424678","DOIUrl":"10.1177/17588359261424678","url":null,"abstract":"<p><strong>Background: </strong>Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). Metastatic tumors to the central nervous system (CNS) are not routinely assessed for the presence of actionable mutations, hence the frequency and concordance of actionable mutations in the cerebrospinal fluid (CSF) versus extracranial sites are not well characterized.</p><p><strong>Objective: </strong>To evaluate the frequency and concordance of actionable mutations in the CSF versus extracranial sites in patients with MBC and LMD.</p><p><strong>Methods: </strong>In this single-center non-therapeutic prospective observational study, we enrolled 15 patients with MBC and known or suspected LMD from 2020 to 2024 and collected CSF, blood, and archival tumor samples. We enumerated CSF circulating tumor cells (CTCs) and analyzed circulating tumor DNA (ctDNA) via next-generation sequencing (NGS) using the CNSide technology (Biocept). When available, we compared CSF NGS results with available NGS data from matched blood and tumor samples.</p><p><strong>Results: </strong>Of the 15 patients enrolled, 14 were determined to have LMD based on CSF cytology, radiographic, and clinical assessment (7 hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-), 6 triple negative breast cancer, 1 HER2+). CSF CTC enumeration was performed in a subset of patients and was positive in 5/7 (71.4%), of which 4/5 had negative CSF cytology. Median CTC enumeration was 0.29 CTCs/mL (range 0-136.4). Of the 14 patients with confirmed LMD, analysis of CSF ctDNA detected pathogenic variants in half of the patients (7/14, 50.0%). Comparison of CSF versus blood and/or tissue-based NGS testing was available for 10 patients: 5 patients (50%) had concordant CSF versus extracranial mutations, 3 patients (30%) had discordant CSF versus extracranial mutations, and 2 patients (20%) had both concordant and discordant CSF versus extracranial mutations.</p><p><strong>Conclusion: </strong>CSF CTCs can be detected and enumerated in patients with MBC and LMD, even in patients with negative CSF cytology. We were able to detect pathogenic mutations in the CSF ctDNA in half of the patients. We observed variable concordance and heterogeneity in the detection of actionable mutations between the CSF, blood, and tumor tissue, supporting the value of investigating the CSF to identify novel targets and resistance mechanisms. Larger studies are needed to assess the clinical utility of these observations, particularly with the development of novel targeted CNS-penetrant agents.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261424678"},"PeriodicalIF":4.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514831","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":"Molecular profile and targeted therapies for ovarian clear cell ovarian cancer.","authors":"Manavi Sachdeva, David S P Tan","doi":"10.1177/17588359261425693","DOIUrl":"10.1177/17588359261425693","url":null,"abstract":"<p><p>Ovarian clear cell carcinoma (OCCC) is a distinct epithelial ovarian cancer subtype with unique molecular features, and a notable resistance to conventional platinum-based chemotherapy in advanced disease. Key molecular hallmarks include frequent <i>ARID1A</i> loss and <i>PIK3CA</i> activation, which often co-occur and contribute to early tumorigenesis. Emerging targeted therapies-including anti-angiogenic agents, immune checkpoint inhibitors, <i>ATR</i> and <i>PI3K</i> pathway inhibitors, and antibody-drug conjugates-demonstrate promising activity, particularly in molecularly defined subgroups, though most evidence to date remains largely limited to early-phase trials. Given its rarity, chemoresistance, and underrepresentation in large trials, OCCC requires histology-specific therapeutic strategies informed by molecular profiling. Ongoing research into biomarker-driven therapies and combination regimens holds the potential to transform outcomes for this challenging ovarian cancer subtype.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261425693"},"PeriodicalIF":4.2,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514798","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 in prostate cancer: current landscape and future directions.","authors":"Zeynep Irem Ozay, Chadi Hage Chehade, Georges Gebrael, Micah Ostrowski, Nicolas Sayegh, Umang Swami, Neeraj Agarwal","doi":"10.1177/17588359261424672","DOIUrl":"10.1177/17588359261424672","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic option, combining the specificity of monoclonal antibodies with the potency of cytotoxic payloads. While initially developed for hematologic and select solid malignancies, advances in antigen discovery, linker chemistry, and payload design have expanded their application to metastatic castration-resistant prostate cancer, where treatment options remain limited. Prostate-specific membrane antigen (PSMA), STEAP-1, TROP-2, CD46, Nectin-4, tissue factor, B7-H3, and DLL3 have emerged as clinically relevant targets, with multiple ADCs evaluated in early and late-phase trials. Although early-generation drugs were hindered by modest efficacy and significant toxicity due to linker instability and off-target effects, some novel ADCs have shown improved tolerability and encouraging antitumor activity. Ongoing studies are exploring rational combinations with hormonal, other targeted, and immune-based therapies to enhance efficacy, overcome resistance, and expand the role of ADCs in advanced prostate cancer. Herein, we provide a comprehensive overview of the clinical development of ADCs in advanced prostate cancer.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261424672"},"PeriodicalIF":4.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514296","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":"Predictive biomarkers of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.","authors":"Juan Francisco Grau Béjar, Elisa Yaniz Galende, Catherine Genestie, Félix Blanc-Durand, Audrey Le Formal, Étienne Rouleau, Alexandra Leary","doi":"10.1177/17588359261423888","DOIUrl":"10.1177/17588359261423888","url":null,"abstract":"<p><p>The introduction of immune checkpoint inhibitors (ICIs) has represented a major therapeutic breakthrough for patients with mismatch repair-deficient (MMRd) endometrial cancer (EC). However, despite initial clinical success, a considerable subset of patients does not experience meaningful clinical benefit from these therapies. The lack of accurate predictive biomarkers to differentiate responders from non-responders remains a key clinical challenge. There is a pressing need for robust predictors of response that can more reliably identify patients with MMRd EC who are unlikely to benefit from ICIs, thereby guiding treatment decisions in routine practice and refining patient stratification in future clinical trials. A range of potential biomarkers has been explored in this context, including genomic, epigenomic, transcriptomic, and proteomic features of both the tumor and its microenvironment. In this review, we evaluate the predictive utility of conventional biomarkers, namely, programmed death-ligand 1 expression and tumor mutation burden, and survey emerging candidates, including proteomic immune signatures, for predicting response or resistance to ICIs in the MMRd EC population. We also examine machine-learning approaches that integrate multi-omics and clinicopathological data to improve stratification, and consider how mechanistic insights into ICI resistance may inform novel therapeutic strategies.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261423888"},"PeriodicalIF":4.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463999","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 in breast oncology: new standards, emerging challenges, and future directions.","authors":"Prarthna V Bhardwaj, Paolo Tarantino, Ilana Schlam","doi":"10.1177/17588359261432056","DOIUrl":"10.1177/17588359261432056","url":null,"abstract":"","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261432056"},"PeriodicalIF":4.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463850","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":"Evaluating Claudin-6 and isochromosome 12p in the progression from germ cell neoplasia in situ to primary testicular germ cell tumor and post-chemotherapy teratoma: implications for CLDN6-targeted therapies.","authors":"Ciara Conduit, Bruno Valentin Sinn, Catherine Mitchell, Jonas Leichsenring, Mark Laible, Kristina Zlatic, Miku Kuba, Sophie O'Haire, Stefan Wöll, Anna Melissa Schlitter, Ben Tran","doi":"10.1177/17588359261421810","DOIUrl":"10.1177/17588359261421810","url":null,"abstract":"<p><strong>Background: </strong>Despite advancements in treatment of advanced testicular germ cell tumors (GCT), metastatic teratoma remains a significant challenge due to its intrinsic chemo- and radioresistance. Claudin-6 (CLDN6), a tumor-specific antigen, has shown promise in targeted therapies for various solid tumors, including metastatic GCT in early phase trials. Testicular GCT frequently exhibit a unique cytogenetic hallmark, isochromosome 12p (i12p), which is associated with tumor development and progression, underscoring its significance in oncogenesis and diagnosis, and potential as a potential biomarker.</p><p><strong>Objectives: </strong>We aimed to understand the expression of CLDN6 during progression from germ cell neoplasia in situ (GCNIS) to primary GCT and postchemotherapy teratoma, and to investigate persistence of i12p in postchemotherapy teratoma.</p><p><strong>Design: </strong>An observational cohort study.</p><p><strong>Methods: </strong>Using matched pre- and postchemotherapy formalin-fixed paraffin-embedded tumor tissue from patients with primary GCT and postchemotherapy teratoma identified from a national GCT registry, iTestis, CLDN6 expression, and presence of i12p were evaluated.</p><p><strong>Results: </strong>Twenty-two patients were eligible. The majority were diagnosed with mixed primary GCT (20/22, 91%) with teratoma the sole histologic component in 86% of postchemotherapy samples (19/22). CLDN6 expression was consistently observed in GCNIS (16/16, 100%) and primary nonteratoma GCT (20/20, 100%) though significantly lower in primary teratoma components (4/10, 40%) and metastatic teratomas (5/22, 23%). The mean proportion of CLDN6-positive cells was higher in primary nonteratoma components (87.5%) compared to primary (6.5%) and postchemotherapy teratoma (4.6%). i12p was also common in primary GCT (18/22, 82%), including pure teratoma (2/2, 100%), though concordance between i12p in primary orchidectomy and metastatic samples was lower (13/18, 72%).</p><p><strong>Conclusion: </strong>Our results demonstrate early overexpression of CLDN6 in GCNIS and high expression in nonteratoma components in primary GCTs, but limited expression in primary and posttreatment teratomas. CLDN6-targeted therapies may not be effective for teratoma. In contrast, i12p was prevalent across all stages of GCT progression, suggesting its potential as a biomarker for identifying viable GCT.</p>","PeriodicalId":23053,"journal":{"name":"Therapeutic Advances in Medical Oncology","volume":"18 ","pages":"17588359261421810"},"PeriodicalIF":4.2,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463832","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}