Clinical Cancer Research最新文献

筛选
英文 中文
Phase 2 pilot trial of tislelizumab plus low-dose nab-paclitaxel for extensive very high-risk non-muscle-invasive bladder cancer
IF 11.5 1区 医学
Clinical Cancer Research Pub Date : 2025-01-07 DOI: 10.1158/1078-0432.ccr-24-3321
Yunkai Qie, Shiwang Huang, Chong Shen, Zhouliang Wu, La Da, Kaipeng Jia, Zhe Zhang, Gangjian Zhao, Lili Wang, Guoping Xu, Yang Zhao, Rui Liang, Jianing Guo, Changping Li, Hua Dong, Man Li, Hongjun Li, Houyuan Chen, Dawei Tian, Changli Wu, Wei Zhang, Zesheng An, Haitao Wang, Yuanjie Niu, Hailong Hu
{"title":"Phase 2 pilot trial of tislelizumab plus low-dose nab-paclitaxel for extensive very high-risk non-muscle-invasive bladder cancer","authors":"Yunkai Qie, Shiwang Huang, Chong Shen, Zhouliang Wu, La Da, Kaipeng Jia, Zhe Zhang, Gangjian Zhao, Lili Wang, Guoping Xu, Yang Zhao, Rui Liang, Jianing Guo, Changping Li, Hua Dong, Man Li, Hongjun Li, Houyuan Chen, Dawei Tian, Changli Wu, Wei Zhang, Zesheng An, Haitao Wang, Yuanjie Niu, Hailong Hu","doi":"10.1158/1078-0432.ccr-24-3321","DOIUrl":"https://doi.org/10.1158/1078-0432.ccr-24-3321","url":null,"abstract":"Purpose: Combinations of immune checkpoint inhibitors and nab-paclitaxel have improved outcomes in advanced urothelial carcinoma and muscle-invasive bladder cancer. This study evaluates the safety and efficacy of tislelizumab combined with low-dose nab-paclitaxel in extensive very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC). Patients and Methods: TRUCE-02 was a single-arm phase 2 trial that included 63 patients with visually incomplete resection and/or high-volume high-grade T1 tumors (with or without carcinoma in situ), who were ineligible for or declined radical cystectomy. Patients received intravenous tislelizumab (200 mg on day 1) and nab-paclitaxel (200 mg on day 2) every 3 weeks, with assessment approximately 3 months after initial administration. The primary endpoint was the complete response rate of high-risk disease. Main secondary endpoints included safety and duration of complete response. Results: The safety analysis included all 63 patients and the efficacy analysis included 59 patients. Thirty-seven patients [62.7%; 95% confidence interval (CI), 49.1-75.0%] achieved a complete response of high-risk disease, with a 24-month sustained response rate of 96.3% (95% CI, 89.4-100.0%). Grade 3-4 treatment-related adverse events occurred in nine patients (14%), with no fatal events reported. Conclusions: Tislelizumab plus low-dose nab-paclitaxel was well-tolerated and showed promising antitumor activity, making it a potential alternative for extensive VHR NMIBC patients who are ineligible for or decline radical cystectomy.","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":"32 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Update on Surveillance Guidelines in Emerging Wilms Tumor Predisposition Syndromes. 新出现的威尔姆斯肿瘤易感综合征的监测指南更新。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-2488
Jack J Brzezinski, Kerri D Becktell, Gaëlle Bougeard, Garrett M Brodeur, Lisa R Diller, Andrea S Doria, Jordan R Hansford, Wendy K Kohlmann, Christian P Kratz, Suzanne P MacFarland, Kristian W Pajtler, Surya P Rednam, Jaclyn Schienda, Lisa J States, Anita Villani, Rosanna Weksberg, Kristin Zelley, Gail E Tomlinson, Jennifer M Kalish
{"title":"Update on Surveillance Guidelines in Emerging Wilms Tumor Predisposition Syndromes.","authors":"Jack J Brzezinski, Kerri D Becktell, Gaëlle Bougeard, Garrett M Brodeur, Lisa R Diller, Andrea S Doria, Jordan R Hansford, Wendy K Kohlmann, Christian P Kratz, Suzanne P MacFarland, Kristian W Pajtler, Surya P Rednam, Jaclyn Schienda, Lisa J States, Anita Villani, Rosanna Weksberg, Kristin Zelley, Gail E Tomlinson, Jennifer M Kalish","doi":"10.1158/1078-0432.CCR-24-2488","DOIUrl":"10.1158/1078-0432.CCR-24-2488","url":null,"abstract":"<p><p>Wilms tumors are commonly associated with predisposition syndromes. Many of these syndromes are associated with specific phenotypic features and are discussed in the related article from the AACR Pediatric Cancer Working Group. Guidelines for surveillance in this population were published in 2017, but since then several studies have identified new genes with recurrent pathogenic variants associated with increased risk for Wilms tumor development. In general, variants in these genes are less likely to be associated with other phenotypic features. Recently, members of the AACR Pediatric Cancer Working Group met to update surveillance guidelines for patients with a predisposition to Wilms tumors with a review of recently published evidence and risk estimates. Risk estimates for Wilms tumor for the more recently described genes are discussed here along with suggested surveillance guidelines for these populations. Several other emerging clinical scenarios associated with Wilms tumor predisposition are also discussed, including patients with family histories of Wilms tumor and no identified causative gene, patients with bilateral tumors, and patients with somatic mosaicism for chromosome 11p15.5 alterations. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors, and other health care professionals on emerging evidence and harmonize updated surveillance recommendations in the North American and Australian context for patients with emerging forms of Wilms tumor predisposition.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"18-24"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes. 由研究者发起的奥拉帕利和替莫唑胺治疗SCLC的I/II期研究:最终分析和中枢神经系统结果
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-2350
Catherine B Meador, Subba R Digumarthy, Beow Y Yeap, Yin P Hung, Mari Mino-Kenudson, Anna F Farago, Rebecca S Heist, J Paul Marcoux, Deepa Rangachari, David A Barbie, Zofia Piotrowska
{"title":"Phase I/II Investigator-Initiated Study of Olaparib and Temozolomide in SCLC: Final Analysis and CNS Outcomes.","authors":"Catherine B Meador, Subba R Digumarthy, Beow Y Yeap, Yin P Hung, Mari Mino-Kenudson, Anna F Farago, Rebecca S Heist, J Paul Marcoux, Deepa Rangachari, David A Barbie, Zofia Piotrowska","doi":"10.1158/1078-0432.CCR-24-2350","DOIUrl":"10.1158/1078-0432.CCR-24-2350","url":null,"abstract":"<p><strong>Purpose: </strong>Temozolomide plus PARP inhibition has shown promise in small cell lung cancer (SCLC). We previously reported outcomes from the first 50 patients (cohort 1) of a phase I/II trial of olaparib/temozolomide in recurrent SCLC. In this study, we report a final analysis of this trial, including a second cohort with an alternate dosing strategy and an exploratory analysis of central nervous system (CNS)-specific outcomes.</p><p><strong>Patients and methods: </strong>This was an open-label phase I/II trial testing the combination of olaparib and temozolomide in relapsed SCLC. The primary endpoint was objective response rate (ORR). Secondary endpoints were safety, progression-free survival, and overall survival. We tested escalating doses of olaparib/temozolomide across two cohorts, both of which had temozolomide dosed on days 1 to 7 of each 21-day cycle. In previously published cohort 1, olaparib was dosed on days 1 to 7; in cohort 2, olaparib was dosed continuously.</p><p><strong>Results: </strong>Sixty-six patients were enrolled across the two cohorts: 50 in cohort 1 and 16 in cohort 2. The confirmed ORR of cohort 1 was 41.7% (20/48 evaluable), and the confirmed ORR of cohort 2 was 7% (1/14 evaluable; closed after dose escalation to enrollment for lack of observed efficacy). Among 15/66 patients (22.7%) with untreated brain metastases at enrollment, the best overall intracranial response was complete response in 6/15 patients, partial response in 4/15 patients, and stable disease in 3/15 patients for a CNS disease control rate of 87% (95% confidence interval, 59.5%-98.3%).</p><p><strong>Conclusions: </strong>Olaparib/temozolomide may be effective in relapsed SCLC, especially for patients with CNS disease. Ongoing analyses with regard to optimal dosing schedule will inform potential for future use of this combination in SCLC.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"25-34"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mucin5AC promotes breast cancer brain metastasis through cMET/CD44v6.
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-1977
Shailendra Kumar Maurya, Jenny A Jaramillo-Gomez, Asad Ur Rehman, Shailendra Kumar Gautam, Mahek Fatima, Md Arafat Khan, Mohd Ali Abbas Zaidi, Parvez Khan, Laiba Anwar, Zahraa Wajih Alsafwani, Ranjana K Kanchan, Sameer Mohiuddin, Ramesh Pothuraju, Raghupathy Vengoji, Ramakanth Chirravuri Venkata, Gopalakrishnan Natarajan, Rakesh Bhatia, Pranita Atri, NaveenKumar Perumal, Sanjib Chaudhary, Imayavaramban Lakshmanan, Sidharth Mahapatra, Geoffrey A Talmon, Jesse L Cox, Lynette M Smith, Juan A Santamaria-Barria, Apar Kishor Ganti, Jawed Akhtar Siddiqui, Diana M Cittelly, Surinder Kumar Batra, Mohd Wasim Nasser
{"title":"Mucin5AC promotes breast cancer brain metastasis through cMET/CD44v6.","authors":"Shailendra Kumar Maurya, Jenny A Jaramillo-Gomez, Asad Ur Rehman, Shailendra Kumar Gautam, Mahek Fatima, Md Arafat Khan, Mohd Ali Abbas Zaidi, Parvez Khan, Laiba Anwar, Zahraa Wajih Alsafwani, Ranjana K Kanchan, Sameer Mohiuddin, Ramesh Pothuraju, Raghupathy Vengoji, Ramakanth Chirravuri Venkata, Gopalakrishnan Natarajan, Rakesh Bhatia, Pranita Atri, NaveenKumar Perumal, Sanjib Chaudhary, Imayavaramban Lakshmanan, Sidharth Mahapatra, Geoffrey A Talmon, Jesse L Cox, Lynette M Smith, Juan A Santamaria-Barria, Apar Kishor Ganti, Jawed Akhtar Siddiqui, Diana M Cittelly, Surinder Kumar Batra, Mohd Wasim Nasser","doi":"10.1158/1078-0432.CCR-24-1977","DOIUrl":"https://doi.org/10.1158/1078-0432.CCR-24-1977","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer (BC) brain metastasis (BrM) remains a significant clinical problem. Mucins have been implicated in metastasis; however, if they are also involved in BCBrM remains unknown. We queried BrM patient databases and found Mucin 5AC (MUC5AC) to be upregulated and therefore sought to define the role of MUC5AC in BCBrM.</p><p><strong>Experimental design: </strong>In-silico dataset analysis, RNA-sequence profiling on patients and cell lines, analysis of patients' serum samples, and in-vitro/vivo knockdown experiments were performed to determine the function of MUC5AC in BCBrM. Coimmunoprecipitation unravels the interactions that can be therapeutically targeted.</p><p><strong>Results: </strong>Global in-silico transcriptomic analysis showed that MUC5AC is significantly higher in BCBrM patients. Archived BCBrM tissue analysis further revealed significantly higher expression of MUC5AC in all BC subtypes, and high MUC5AC expression predicted poor survival in HER2+ BCBrM. We validated these observations in BCBrM cell lines and tissue samples. Interestingly, elevated levels of MUC5AC were detected in the sera of BCBrM patients. MUC5AC silencing in BCBrM cells reduced migration, adhesion, and reduced BrM in experimental intracardiac injection mouse model. We found high expression of cMET and CD44v6 in BCBrM, which increased MUC5AC expression via HGF signaling. MUC5AC interacts with cMET and CD44v6, suggesting that MUC5AC promotes BCBrM via the cMET/CD44v6 axis. This axis can be targeted with c-MET inhibitor Bozitinib (PLB1001) to inhibit BCBrM.</p><p><strong>Conclusions: </strong>Our study establishes that the MUC5AC/cMET/CD44v6 axis is critical for BCBrM, and blocking this axis will be a novel therapeutic approach for BCBrM.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":""},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial. 肠道亚型作为局部晚期胃腺癌新辅助免疫化疗反应的生物标志物:一项前瞻性II期试验的启示。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-2436
Lei Wang, Mengting Sun, Jinyang Li, Linghong Wan, Yuting Tan, Shuoran Tian, Yongying Hou, Linyu Wu, Ziyi Peng, Xiao Hu, Qihua Zhang, Zening Huang, Mengyi Han, Shiyin Peng, Yuwei Pan, Yuanfeng Ren, Mengsi Zhang, Dongfeng Chen, Qin Liu, Xianfeng Li, Zhong-Yi Qin, Junyv Xiang, Mengxia Li, Jianwu Zhu, Qiyue Chen, Huiyan Luo, Shunan Wang, Tao Wang, Fan Li, Xiu-Wu Bian, Bin Wang
{"title":"Intestinal Subtype as a Biomarker of Response to Neoadjuvant Immunochemotherapy in Locally Advanced Gastric Adenocarcinoma: Insights from a Prospective Phase II Trial.","authors":"Lei Wang, Mengting Sun, Jinyang Li, Linghong Wan, Yuting Tan, Shuoran Tian, Yongying Hou, Linyu Wu, Ziyi Peng, Xiao Hu, Qihua Zhang, Zening Huang, Mengyi Han, Shiyin Peng, Yuwei Pan, Yuanfeng Ren, Mengsi Zhang, Dongfeng Chen, Qin Liu, Xianfeng Li, Zhong-Yi Qin, Junyv Xiang, Mengxia Li, Jianwu Zhu, Qiyue Chen, Huiyan Luo, Shunan Wang, Tao Wang, Fan Li, Xiu-Wu Bian, Bin Wang","doi":"10.1158/1078-0432.CCR-24-2436","DOIUrl":"10.1158/1078-0432.CCR-24-2436","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant immunochemotherapy (NAIC) markedly induces pathologic regression in locally advanced gastric adenocarcinoma. However, specific biomarkers are still lacking to effectively identify the beneficiary patients for NAIC.</p><p><strong>Patients and methods: </strong>A prospective, single-arm, phase II study was conducted to treat locally advanced gastric adenocarcinoma with NAIC (NCT05515796). Correlation between clinicopathologic characteristics and neoadjuvant efficacy was investigated. Bulk RNA sequencing data from 104 samples (from 75 patients in two independent cohorts) and single-cell RNA sequencing data from 105 treatment-naïve gastric adenocarcinomas were comprehensively analyzed to decipher the association of epithelial and microenvironmental characteristics and clinical responses.</p><p><strong>Results: </strong>The prespecified primary endpoints were achieved: pathologic complete regression rate was 30%, major pathologic regression rate was 43%, and the regimen was well tolerated. Analysis of baseline clinical-pathologic parameters revealed the intestinal subtype of Lauren's classification as a key feature stratifying patients with increased sensitivity to NAIC. Mechanistically, an increased pool of DNA damage repair-active cancer cells and enrichment of CLEC9A+ dendritic cells in the tumor microenvironment were associated with enhanced responsiveness of the intestinal subtype gastric adenocarcinoma to NAIC. More importantly, an intestinal subtype-specific signature model was constructed by the machine learning algorithm NaiveBayes via integrating the transcriptomic features of both DNA damage repair-active cancer cells and CLEC9A+ dendritic cells, which accurately predicted the efficacy of NAIC in multiple independent gastric adenocarcinoma cohorts.</p><p><strong>Conclusions: </strong>Intestinal subtype is a histologic biomarker of enhanced sensitivity of gastric adenocarcinoma to NAIC. The intestinal subtype-specific signature model is applicable to guide NAIC for patients with locally advanced gastric adenocarcinoma.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"74-86"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer. 化疗促使转移性卵巢癌出现三级淋巴结构,这些结构与 ICI 反应性 TCF1+CD8+ T 细胞相关。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-1594
Tereza Lanickova, Michal Hensler, Lenka Kasikova, Sarka Vosahlikova, Artemis Angelidou, Josef Pasulka, Hannah Griebler, Jana Drozenova, Katerina Mojzisova, Ann Vankerckhoven, Jan Laco, Ales Ryska, Pavel Dundr, Roman Kocian, David Cibula, Tomas Brtnicky, Petr Skapa, Francis Jacob, Marek Kovar, Ivan Praznovec, Iain A McNeish, Michal J Halaska, Lukas Rob, An Coosemans, Sandra Orsulic, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
{"title":"Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer.","authors":"Tereza Lanickova, Michal Hensler, Lenka Kasikova, Sarka Vosahlikova, Artemis Angelidou, Josef Pasulka, Hannah Griebler, Jana Drozenova, Katerina Mojzisova, Ann Vankerckhoven, Jan Laco, Ales Ryska, Pavel Dundr, Roman Kocian, David Cibula, Tomas Brtnicky, Petr Skapa, Francis Jacob, Marek Kovar, Ivan Praznovec, Iain A McNeish, Michal J Halaska, Lukas Rob, An Coosemans, Sandra Orsulic, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova","doi":"10.1158/1078-0432.CCR-24-1594","DOIUrl":"10.1158/1078-0432.CCR-24-1594","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication.</p><p><strong>Experimental design: </strong>We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts.</p><p><strong>Results: </strong>We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden.</p><p><strong>Conclusions: </strong>Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC. See related commentary by Bravo Melgar and Laoui, p. 10.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"164-180"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FDA Approval Summary: Olutasidenib for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase 1 Mutation. FDA 批准摘要:Olutasidenib 用于异柠檬酸脱氢酶-1 基因突变的复发性或难治性急性髓性白血病成人患者。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-2196
Ashley C Woods, Kelly J Norsworthy, Moran Choe, Brenda J Gehrke, Haiyan Chen, Jonathon Vallejo, Lili Pan, Xiling Jiang, Hongshan Li, Jeffrey Kraft, Jiang Liu, Rosane Charlab, Olanrewaju O Okusanya, Brian Booth, Richard Pazdur, Marc R Theoret, R Angelo de Claro
{"title":"FDA Approval Summary: Olutasidenib for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an Isocitrate Dehydrogenase 1 Mutation.","authors":"Ashley C Woods, Kelly J Norsworthy, Moran Choe, Brenda J Gehrke, Haiyan Chen, Jonathon Vallejo, Lili Pan, Xiling Jiang, Hongshan Li, Jeffrey Kraft, Jiang Liu, Rosane Charlab, Olanrewaju O Okusanya, Brian Booth, Richard Pazdur, Marc R Theoret, R Angelo de Claro","doi":"10.1158/1078-0432.CCR-24-2196","DOIUrl":"10.1158/1078-0432.CCR-24-2196","url":null,"abstract":"<p><p>On December 1, 2022, the FDA approved the new molecular entity olutasidenib (Rezlidhia, Rigel Pharmaceuticals), a small-molecule inhibitor of isocitrate dehydrogenase 1, for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible isocitrate dehydrogenase 1 mutation as detected by an FDA-approved test. The efficacy of olutasidenib was established based on complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion of transfusion dependence to transfusion independence in Study 2102-HEM-101. In the pivotal trial, 147 adult patients treated with 150 mg twice daily of olutasidenib were evaluable for efficacy. With a median follow-up of 10.2 months, the CR/CRh rate was 35% (95% confidence interval, 27%-43%), with a median duration of response of 25.9 months [95% confidence interval, 13.5-not reached]. Of the 86 patients who were transfusion dependent at baseline, 29 became transfusion independent (34%). The most common (≥20%) adverse reactions were nausea, fatigue, arthralgia, leukocytosis, dyspnea, pyrexia, rash, mucositis, diarrhea, and transaminitis. An assessment of long-term safety of olutasidenib is a condition of this approval.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"12-17"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic and Epigenomic Analysis of Plasma Cell-Free DNA Identifies Stemness Features Associated with Worse Survival in Lethal Prostate Cancer. 血浆细胞游离 DNA 的基因组和表观基因组分析确定了与致死性前列腺癌生存率下降相关的干性特征。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-1658
Pradeep S Chauhan, Irfan Alahi, Savar Sinha, Elisa M Ledet, Ryan Mueller, Jessica Linford, Alexander L Shiang, Jace Webster, Lilli Greiner, Breanna Yang, Gabris Ni, Ha X Dang, Debanjan Saha, Ramandeep K Babbra, Wenjia Feng, Peter K Harris, Faridi Qaium, Dzifa Y Duose, Sanchez E Alexander, Alexander D Sherry, Ellen B Jaeger, Patrick J Miller, Sydney A Caputo, Jacob J Orme, Fabrice Lucien, Sean S Park, Chad Tang, Russell K Pachynski, Oliver Sartor, Christopher A Maher, Aadel A Chaudhuri
{"title":"Genomic and Epigenomic Analysis of Plasma Cell-Free DNA Identifies Stemness Features Associated with Worse Survival in Lethal Prostate Cancer.","authors":"Pradeep S Chauhan, Irfan Alahi, Savar Sinha, Elisa M Ledet, Ryan Mueller, Jessica Linford, Alexander L Shiang, Jace Webster, Lilli Greiner, Breanna Yang, Gabris Ni, Ha X Dang, Debanjan Saha, Ramandeep K Babbra, Wenjia Feng, Peter K Harris, Faridi Qaium, Dzifa Y Duose, Sanchez E Alexander, Alexander D Sherry, Ellen B Jaeger, Patrick J Miller, Sydney A Caputo, Jacob J Orme, Fabrice Lucien, Sean S Park, Chad Tang, Russell K Pachynski, Oliver Sartor, Christopher A Maher, Aadel A Chaudhuri","doi":"10.1158/1078-0432.CCR-24-1658","DOIUrl":"10.1158/1078-0432.CCR-24-1658","url":null,"abstract":"<p><strong>Purpose: </strong>Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood.</p><p><strong>Experimental design: </strong>We applied targeted cell-free DNA (cfDNA) sequencing to 126 patients with mCRPC from three academic cancer centers and separately performed genome-wide cfDNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 patients with mCRPC, respectively, to develop and validate a stem-like signature, which we inferred from cfDNA.</p><p><strong>Results: </strong>Targeted cfDNA sequencing detected AR/enhancer alterations prior to first-line ARSIs that correlated with significantly worse progression-free survival (P = 0.01; HR = 2.12) and overall survival (P = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (P < 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cfDNA revealed enrichment for stemness-associated transcription factors in patients with lethal mCRPC. The resulting stemness signature was then validated in a completely held-out cohort of 80 patients with mCRPC profiled by tumor RNA sequencing.</p><p><strong>Conclusions: </strong>We analyzed a total of 220 patients with mCRPC, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness. See related commentary by Nawfal et al., p. 7.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"151-163"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unearthing a Prostate Cancer cfDNA Signature that "Stems" from AR Alterations. 发现 "源于 "AR 改变的前列腺癌 cfDNA 特征。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-2849
Rashad Nawfal, Razane El Hajj Chehade, Jacob E Berchuck
{"title":"Unearthing a Prostate Cancer cfDNA Signature that \"Stems\" from AR Alterations.","authors":"Rashad Nawfal, Razane El Hajj Chehade, Jacob E Berchuck","doi":"10.1158/1078-0432.CCR-24-2849","DOIUrl":"10.1158/1078-0432.CCR-24-2849","url":null,"abstract":"<p><p>Androgen receptor alterations portend a poor prognosis in patients with advanced prostate cancer. A recent study identified a stemness signature enriched in cell-free DNA from androgen receptor-altered patients, associated with worse outcomes. These findings highlight the potential of epigenomic liquid biopsy tools to discover novel clinically relevant tumor molecular subtypes. See related article by Chauhan et al., p. 151.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"7-9"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrating Molecular Imaging and Transcriptomic Profiling in Advanced HER2-Positive Breast Cancer Receiving Trastuzumab Emtansine: An Analysis of the ZEPHIR Clinical Trial. 在接受曲妥珠单抗埃坦新(T-DM1)治疗的晚期 HER2 阳性乳腺癌中整合分子成像和转录组分析:ZEPHIR 临床试验分析。
IF 1 1区 医学
Clinical Cancer Research Pub Date : 2025-01-06 DOI: 10.1158/1078-0432.CCR-24-1007
Mattia Rediti, Danai Fimereli, Magdalena Mileva, Zéna Wimana, David Venet, Patrick Flamen, Thomas Guiot, Elisabeth G E de Vries, Carolien P Schröder, Catharina Willemien Menke-van der Houven van Oordt, Marion Maetens, Samira Majjaj, Denis Larsimont, Françoise Rothé, Christos Sotiriou, Géraldine Gebhart
{"title":"Integrating Molecular Imaging and Transcriptomic Profiling in Advanced HER2-Positive Breast Cancer Receiving Trastuzumab Emtansine: An Analysis of the ZEPHIR Clinical Trial.","authors":"Mattia Rediti, Danai Fimereli, Magdalena Mileva, Zéna Wimana, David Venet, Patrick Flamen, Thomas Guiot, Elisabeth G E de Vries, Carolien P Schröder, Catharina Willemien Menke-van der Houven van Oordt, Marion Maetens, Samira Majjaj, Denis Larsimont, Françoise Rothé, Christos Sotiriou, Géraldine Gebhart","doi":"10.1158/1078-0432.CCR-24-1007","DOIUrl":"10.1158/1078-0432.CCR-24-1007","url":null,"abstract":"<p><strong>Purpose: </strong>The ZEPHIR clinical trial evaluated the role of [89Zr]trastuzumab-PET/CT (HER2-PET/CT) and 2-[18F]fluoro-2-deoxy-D-glucose PET/CT ([18F]FDG-PET/CT) in predicting outcomes in patients with advanced HER2-positive breast cancer treated with trastuzumab emtansine (T-DM1). In this study, we combined molecular/metabolic imaging and transcriptomic data to investigate the biological processes associated with [89Zr]trastuzumab and [18F]FDG uptake and to dissect the mechanisms involved in T-DM1 resistance.</p><p><strong>Experimental design: </strong>RNA was extracted from metastasis biopsies obtained in the ZEPHIR trial. HER2-PET/CT and [18F]FDG-PET/CT imaging data of biopsied lesions were integrated with transcriptomic data. Lesions were compared based on the level of [89Zr]trastuzumab uptake as well as on the presence/absence of metabolic response, defined comparing baseline and on-treatment [18F]FDG-PET/CT.</p><p><strong>Results: </strong>We analyzed matched transcriptomic and molecular/metabolic imaging data for 24 metastases. Genes and pathways involved in extracellular matrix (ECM) organization and glycosylphosphatidylinositol synthesis were enriched in lesions presenting low [89Zr]trastuzumab uptake. [18F]FDG uptake at baseline correlated with proliferation and immune-related processes. Hypoxia and ECM-related processes were enriched in lesions showing no metabolic response to T-DM1, whereas immune-related processes were associated with high [89Zr]trastuzumab uptake and metabolic response. Gene signatures including differentially expressed genes according to [89Zr]trastuzumab uptake and metabolic response showed predictive value in an external cohort.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this study represents the first correlative analysis between [89Zr]trastuzumab tumor uptake and gene expression profiling in humans. Our findings suggest a role for ECM in impairing [89Zr]trastuzumab tumor uptake and T-DM1 metabolic response in advanced HER2-positive breast cancer, highlighting the potential of molecular imaging to depict tumor microenvironment features.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":" ","pages":"110-121"},"PeriodicalIF":10.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信