Cancer research communications最新文献

{"title":"IMGN853 Induces Autophagic Cell Death in Combination Therapy for Ovarian Cancer.","authors":"Anca Chelariu-Raicu, Thanh Chung Vu, Sujanitha Umamaheswaran, Elaine Stur, Pahul Hanjra, Yunah Han, Min Hu, Jerome Lin, Barrett C Lawson, Jinsong Liu, Anil K Sood, Yunfei Wen","doi":"10.1158/2767-9764.CRC-24-0215","DOIUrl":"10.1158/2767-9764.CRC-24-0215","url":null,"abstract":"<p><strong>Significance: </strong>FOLR1 is heterogeneously overexpressed in epithelial ovarian cancer. We examined the combined effects of the anti-FOLR1 antibody-drug conjugate (IMGN853) with other drugs, including topotecan, anti-VEGF-A antibody, and olaparib. These findings could contribute to the continued development of IMGN853 in the treatment of ovarian cancer.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"512-526"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"23ME-01473, an Fc Effector-Enhanced Anti-ULBP6/2/5 Antibody, Restores NK Cell-Mediated Antitumor Immunity through NKG2D and FcγRIIIa Activation.","authors":"Joel S Benjamin, Abigail Jarret, Shashank Bharill, Pierre Fontanillas, Shruti Yadav, Debasish Sen, Dina Ayupova, Danielle Kellar, Susanne Tilk, Clifford Hom, Zahra Bahrami Dizicheh, I-Ling Chen, Anh N Diep, Shi Shi, Nives Ivic, Caroline Bonnans, Alex Owyang, Pranidhi Sood, Germaine Fuh, Maike Schmidt, Kimberline Y Gerrick, Patrick Koenig, Mauro Poggio","doi":"10.1158/2767-9764.CRC-24-0478","DOIUrl":"10.1158/2767-9764.CRC-24-0478","url":null,"abstract":"<p><strong>Significance: </strong>This study emphasizes the utility of population-based genome-wide assessments for discovering naturally occurring genetic variants associated with lifetime risks for cancer or immune diseases as novel drug targets. We identify ULBP6 as a potential keystone member of the NKG2D pathway, which is important for antitumor immunity. Targeting ULBP6 may hold therapeutic promise for patients with cancer.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":"5 3","pages":"476-495"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Checkpoint Reversal Receptor Mediates Bipartite Activation and Enhances CAR T-cell Function.","authors":"Daniel Landi, Shoba A Navai, Rebecca M Brock, Kristen Fousek, Zeid Nawas, Khaled Sanber, Cynthia Chauvin-Fleurence, Raksha R Bhat, Shuo Xu, Purna Krishnamurthy, Michelle Choe, Matthew E Campbell, Jessica S Morris, Ahmed Z Gad, Ankita Shree, Alesandra S Echeandia Marrero, Amr M Saadeldin, Pretty R Matthew, Dolores Mullikin, Kevin Bielamowicz, Lyazat Kurenbekova, Angela M Major, Vita S Salsman, Tiara T Byrd, John M Hicks, Yi Jonathan Zhang, Jason Yustein, Alexandre F Carisey, Sujith K Joseph, Nabil Ahmed, Meenakshi Hegde","doi":"10.1158/2767-9764.CRC-24-0125","DOIUrl":"10.1158/2767-9764.CRC-24-0125","url":null,"abstract":"<p><strong>Significance: </strong>Enhancing CART function and persistence while balancing immune effector-mediated inflammation is crucial. Using our clinically relevant HER2-CAR platform, we demonstrate that tumor-intrinsic signals like the PD-1/PD-L1 immune checkpoint can be leveraged in CART design to modulate immune synapse and metabolic parameters, improving antitumor function without increasing cytokine production.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"527-548"},"PeriodicalIF":2.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional profiling of p53 and RB cell cycle regulatory proficiency suggests mechanism-driven molecular stratification in endometrial carcinoma.","authors":"Zelei Yang, Saie Mogre, Hyeji Jun, Ruiyang He, Sneha Ghosh Chaudhary, Upendra Raj Bhattarai, Shannan J Ho Sui, Ursula A Matulonis, Suzan Lazo, Aniket Shetty, Amy Cameron, Quang-De Nguyen, Sarah J Hill","doi":"10.1158/2767-9764.CRC-24-0028","DOIUrl":"10.1158/2767-9764.CRC-24-0028","url":null,"abstract":"<p><p>In the United States, Endometrial carcinoma (EC) is the most frequently occurring gynecologic cancer. Many ECs harbor mutations in cell cycle regulatory genes including TP53 and RB1, amongst others. RB and p53 both regulate the G1/S transition while p53 also regulates the G2/M transition and mitotic progression, all of which rely on targetable regulatory kinases. It is likely that many ECs harbor targetable defects in some aspect of cell cycle regulation, but there has been no profiling of p53- or RB- linked cell cycle functional capacity and corresponding therapeutic vulnerabilities in EC cells. Here, we utilize functional and transcriptomic assays on a panel of EC cell lines and patient-derived organoids to characterize the p53 and RB cell cycle regulatory proficiency and linked therapeutic vulnerabilities in EC. We show that TP53 genomic and functional status has poor predictive capacity for EC therapeutic response. Rather, proper RB regulation correlates with response to G1/S targeting CDK4/6 inhibitors, and dysfunction in regulation of mitotic progression correlates with response to Aurora kinase B inhibitors. A subset of TP53 mutant ECs are RB1 wild type, express RB protein, have intact RB regulation, and are sensitive to CDK4/6 inhibitors, suggesting that excluding patients from emerging CDK4/6 inhibitor trials based on aggressive histology or TP53 status should be reconsidered. These findings were validated in vivo in xenograft models. These results can expand current EC molecular stratification to include mechanism-driven subtypes and suggest clinical trials of novel targeted therapies based on biologic understanding for advanced or recurrent EC patients.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Melanoma Brain Metastasis CTC Signature and CTC:B-cell Clusters Associate with Secondary Liver Metastasis: A Melanoma Brain-Liver Metastasis Axis.","authors":"Tetiana Y Bowley, Mireya C Ortiz, Irina V Lagutina, Mara P Steinkamp, Bridget N Fahy, Bernard Tawfik, Moises Harari-Turquie, Dario Marchetti","doi":"10.1158/2767-9764.CRC-24-0498","DOIUrl":"10.1158/2767-9764.CRC-24-0498","url":null,"abstract":"<p><strong>Significance: </strong>This study provides important insights into the relevance of prometastatic CTC:B-cell clusters in melanoma progression, extends the importance of the CTC RPL/RPS gene signature beyond primary metastasis/melanoma brain metastasis driving targeted organ specificity for liver metastasis (\"metastasis of metastasis\"), and identifies new targets for clinical melanoma metastasis therapies.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"295-308"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic Tracking of Tumor Microenvironment Modulation Using Kaede Photoconvertible Transgenic Mice Unveils New Biological Properties of Viral Immunotherapy.","authors":"Anne R Diers, Qiuchen Guo, Zhi Li, Erin Richardson, Suaad Idris, Claire Willis, Paul P Tak, David R Withers, Francesca Barone","doi":"10.1158/2767-9764.CRC-24-0434","DOIUrl":"10.1158/2767-9764.CRC-24-0434","url":null,"abstract":"<p><strong>Significance: </strong>This study utilized a novel photoconvertible mouse tumor model to track immune cell trafficking upon treatment with an investigational viral immunotherapy (CAN-2409), revealing enhanced T-cell responses after viral immunotherapy associated with local proliferation of T cells within tumors that could further enhance antitumor efficacy in combination with immune checkpoint inhibitors. These findings define temporally and spatially distinct interactions of immune cells that could be harnessed by novel therapeutics.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"327-338"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase Ib Study of Immunocytokine Simlukafusp Alfa (FAP-IL2v) Combined with Pembrolizumab for Treatment of Advanced and/or Metastatic Melanoma.","authors":"Eva Munoz-Couselo, Ainara Soria Rivas, Shahneen Sandhu, Georgina V Long, Miguel F Sanmamed, Anna Spreafico, Elizabeth Buchbinder, Mario Sznol, Hans Prenen, Alexander Fedenko, Mohammed Milhem, Ana Maria Arance Fernandez, Jean-Jacques Grob, Lev Demidov, Caroline Robert, Christin Habigt, Stefan Evers, Nassim Sleiman, David Dejardin, Caroline Ardeshir, Nicole Martin, Christophe Boetsch, Jehad Charo, Volker Teichgräber, Anton Kraxner, Nino Keshelava, Oliver Bechter","doi":"10.1158/2767-9764.CRC-24-0601","DOIUrl":"10.1158/2767-9764.CRC-24-0601","url":null,"abstract":"<p><strong>Purpose: </strong>This study explored the combination of fibroblast activation protein (FAP) IL2 variant (FAP-IL2v), a novel immune-cytokine, with pembrolizumab in patients with advanced and/or metastatic melanoma.</p><p><strong>Patients and methods: </strong>This open-label, multicenter, phase Ib clinical study (NCT03875079) evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics, and antitumor activity of FAP-IL2v (simlukafusp alfa, RO6874281) in combination with pembrolizumab. Patients with advanced and/or metastatic melanoma were either checkpoint inhibitor (CPI)-naïve or CPI-experienced. Patients received 10 mg FAP-IL2v either continuously once every 3 weeks (Q3W) or in an induction/maintenance setting consisting of a 3-week induction phase with weekly (QW) dosing followed by continuous Q3W dosing. Pembrolizumab was dosed Q3W at 200 mg.</p><p><strong>Results: </strong>Eighty-three patients were treated: 16 patients in two safety run-in cohorts and 67 patients in two extension cohorts; 75 (90.4%) patients were CPI-experienced. The pharmacokinetics of FAP-IL2v in combination with pembrolizumab was similar to that after administration as monotherapy. Consistent with the proposed mode of action, FAP-IL2v preferentially expanded NK and CD8 T cells. The most common FAP-IL2v-related grade 3/4 adverse events were lymphopenia (23%), elevated γ-glutamyltransferase (8%), elevated alanine aminotransferase (6%), and infusion-related reaction (6%). A response was observed in 5 of 75 (6.7%) CPI-experienced patients (all partial responses) and 2 of 8 CPI-naïve patients (one complete response and one partial response). The median progression-free survival was 3.1 months.</p><p><strong>Conclusions: </strong>The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in patients with melanoma with prior CPI due to the lack of clinical activity.</p><p><strong>Significance: </strong>In this phase Ib study, the combination of FAP-IL2v, an immune-cytokine developed to overcome the limitations of wild-type IL2, with the CPI pembrolizumab did not show meaningful antitumor activity in patients who had progressed on prior CPI therapy, suggesting that FAP-IL2v alone cannot overcome CPI resistance or unresponsiveness.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"358-368"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stanniocalcin 1 in Patients with Refractory Colorectal Cancer Treated with Regorafenib: A Post Hoc Biomarker Analysis of the TEXCAN and CORRECT Trials.","authors":"Angélique Vienot, Dewi Vernerey, Adeline Bouard, Elodie Klajer, Stefano Kim, Christophe Tournigand, Christophe Louvet, Thierry André, Benoît Rousseau, Mylène Wespiser, Laurie Spehner, Ying A Wang, Anke Weispfenning, Emmanuelle Dochy, Christophe Borg","doi":"10.1158/2767-9764.CRC-24-0246","DOIUrl":"10.1158/2767-9764.CRC-24-0246","url":null,"abstract":"<p><strong>Significance: </strong>STC1 is a protein secreted by intratumor endothelial cells in which plasma concentrations increase in patients with chemorefractory mCRC. Based on analyses of patients with refractory mCRC in the TEXCAN and CORRECT trials, we found that STC1 plasma levels had a prognostic role for OS, with high levels associated with poor outcome. A predictive role for baseline STC1 levels was pointed out for regorafenib efficacy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"287-294"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence.","authors":"Elizabeth S McDonald, Tien-Chi Pan, Dhruv K Pant, Melissa A Troester, Andrew V Kossenkov, David A Mankoff, Robert H Mach, Lewis A Chodosh","doi":"10.1158/2767-9764.CRC-23-0562","DOIUrl":"10.1158/2767-9764.CRC-23-0562","url":null,"abstract":"<p><strong>Significance: </strong>This first large-scale analysis of the putative ternary complex responsible for rapid low-density lipoprotein internalization in breast cancer reveals a link between component expression and recurrence, with prognostic implications for identifying patients needing supplemental posttreatment surveillance and/or additional therapeutic approaches.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"226-239"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP Inhibitors Differentially Regulate Immune Responses in Distinct Genetic Backgrounds of High-Grade Serous Tubo-Ovarian Carcinoma.","authors":"Luiza Doro Pereira, Monica Wielgos-Bonvallet, Selim Misirlioglu, Alireza Khodadai-Jamayran, Petar Jelinic, Douglas A Levine","doi":"10.1158/2767-9764.CRC-24-0515","DOIUrl":"10.1158/2767-9764.CRC-24-0515","url":null,"abstract":"<p><strong>Significance: </strong>This work highlights how different PARPis, especially talazoparib, modulate immune-related gene expression in ovarian cancer cells, independent of the cGAS-STING pathway. These findings may improve our understanding of how different PARPis affect the immune system in various genetic backgrounds.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"339-348"},"PeriodicalIF":2.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}