Cancer research communications最新文献

{"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 Andre, Benoit Rousseau, Mylène Wespiser, Laurie Spehner, Ying A Wang, Anke Weispfenning, Emmanuelle Dochy, Christophe Borg","doi":"10.1158/2767-9764.CRC-24-0246","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0246","url":null,"abstract":"<p><p>Biomarkers for anti-angiogenic drugs in chemo-refractory metastatic colorectal cancer (mCRC) are lacking. We investigated the relationship between stanniocalcin 1 (STC1) and outcomes in patients treated with regorafenib in the TEXCAN and CORRECT trials. Baseline plasma STC1 protein levels were measured by ELISA from patients with chemo-refractory mCRC enrolled in TEXCAN (regorafenib n=48) and CORRECT (placebo n=211; regorafenib n=435). The relationship between STC1 levels and overall survival (OS) was assessed using a Cox proportional hazards model. The median STC1 value was increased in patients with chemo-refractory mCRC (1211 pg/mL) compared with previously untreated patients (215 pg/mL). Using an optimized cut-off, STC1 was prognostic for OS (HR 2.12, 95% CI 1.79, 2.50; P<0.001), with a median OS of 7.63 months in the STC1 low group (<1436.87 pg/mL; n=400) and 3.81 months in the STC1 high group (≥1436.87 pg/mL; n=246). The interaction p-value of LDH and treatment revealed no predictive effect of LDH levels on OS in terms of regorafenib (P=0.598). A predictive analysis suggested a significant association between STC1 and regorafenib for OS (interaction P=0.049). Median OS with regorafenib versus placebo was 8.32 versus 6.54 months in the STC1 low group (HR 0.83, 95% CI 0.66, 1.03; P=0.087) and 4.41 versus 3.09 months in the STC1 high group (HR 0.64, 95% CI 0.49, 0.84; P=0.001), respectively. Altogether, high STC1 protein levels have a predictive potential to characterize a population of patients with chemo-refractory mCRC and poor prognosis in whom regorafenib has an increased level of efficacy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980833","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":"The Selective WEE1 Inhibitor Azenosertib Shows Synergistic Antitumor Activity with KRASG12C Inhibitors in Preclinical Models.","authors":"Nathan M Jameson, Daehwan Kim, Catherine Lee, Blake Skrable, Alexandra Shea, Xiao Guo, Hooman Izadi, Mona Abed, Olivier Harismendy, Jianhui Ma, Doris S Kim, Mark R Lackner","doi":"10.1158/2767-9764.CRC-24-0411","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0411","url":null,"abstract":"<p><p>KRAS is a potent oncogenic driver which results in downstream hyperactivation of MAPK signaling, while simultaneously increasing replication stress (RS) and accumulation of DNA damage. KRASG12C mutations are common and targetable alterations. Therapeutic inhibition of KRASG12C and eventual resistance to these inhibitors are also known to drive RS and DNA damage through adaptive mechanisms that maintain addiction to high MAPK signaling. High levels of RS result in a stronger reliance on cell cycle checkpoints, thereby introducing a vulnerability to inhibition of cell cycle checkpoint regulators such as the WEE1 kinase. This provides rationale for combining azenosertib, a novel, selective, and orally bioavailable WEE1 inhibitor, with KRASG12C inhibitors. In vitro combination of azenosertib with multiple KRASG12C inhibitors demonstrated synergistic cell growth inhibition across a panel of KRASG12C cell lines in both 2D and 3D assays. In vivo studies demonstrated azenosertib exhibited significant monotherapy activity as well as synergistic tumor growth inhibition (TGI) when combined with KRASG12C inhibitors, including tumor regression in CDX models of NSCLC, CRC, and PDAC. Importantly, KRASG12C inhibitor-resistant CDX and PDX models demonstrated synergistic TGI in combination arms. Finally, analysis of biomarkers from in vitro and in vivo tumor samples displayed increases in protein markers of RS, DNA damage, and apoptosis after combination treatment. Taken together, our results suggest that the combination of azenosertib with KRASG12C inhibitors enhances tumor growth inhibition over single agent therapy and may be an effective treatment strategy for patients with KRASG12C tumors.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980836","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":"Real-World Incidence of Anaplastic Lymphoma Kinase alterations in Hispanics with Non-Small Cell Lung Cancer at a Large Academic Institution in Los Angeles.","authors":"Darin Poei, Sana Ali, Jacob S Thomas, Jorge J Nieva, Robert C Hsu","doi":"10.1158/2767-9764.CRC-24-0504","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0504","url":null,"abstract":"<p><p>Race and ethnicity affect the distribution of molecular alterations seen in patients with non-small cell lung cancer (NSCLC). While anaplastic lymphoma kinase (ALK) alterations are known to occur in 4-5% of the population, data specific to the Hispanic population remains limited. This study describes the real-world incidence of ALK alterations in Hispanic patients with NSCLC treated at a large academic institution in Los Angeles, California, USA to further elucidate the underlying factors that shape differences in mutational profiles. 607 non-small cell lung cancer (NSCLC) patients treated at Los Angeles General Medical Center (n=172) and University of Southern California Norris Comprehensive Cancer Center (n=435) who received comprehensive genomic profiling (CGP) were evaluated from January 2015 to June 2023. Fisher's exact test and multivariate logistic regression were incorporated for statistical analysis. Hispanic patients exhibited a higher incidence of ALK alterations (12.76%, n=18/141) compared to non-Hispanic patients (5.36%, n=23/466) (p=0.0046). Multivariate logistic regression showed Hispanic ethnicity HR 2.393 (95% CI 1.115-5.092) and age at diagnosis HR 0.9325 (95% CI 0.9081-0.9558) were significant variables in ALK alteration incidence. 55.81% (n=24) of ALK alterations were initially found via comprehensive genomic profiling (CGP). This study highlights a significantly higher incidence of ALK alterations among Hispanic patients with NSCLC, emphasizing the impact of race and ethnicity on molecular alterations. Future research is required to evaluate this trend in a larger, more diverse cohort and investigate the roles of environmental factors and tumor microenvironments in influencing ALK alteration prevalence.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980820","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":"Analysis of Urban Indian Organizations' Promotion of Cancer Services.","authors":"William O Carson, Alyssa Little, Angela Monetathchi, Jennifer Erdrich, Felina M Cordova-Marks","doi":"10.1158/2767-9764.CRC-24-0335","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-24-0335","url":null,"abstract":"<p><p>The burden of cancer remains elevated for American Indian/Alaska Natives (AI/AN) in the United States, particularly urban communities. Urban Indian Organizations (UIOs) are part of the Indian health care system for urban AI/AN populations to receive culturally competent care; therefore, it is important that UIOs convey the importance of cancer preventive and treatment options through their websites. The purpose of this study was to utilize the Indian Health Service (IHS) Office of Urban Indian Health Programs' official website to identify, analyze, and describe IHS funded UIOs offering cancer-related services. We utilized qualitative content analysis on UIOs with primary care service capabilities. After determination of UIOs, each eligible website was reviewed to determine if promotion of specific cancer related services was being done based on the following categories: primary prevention, cancer screening, cancer support, and information/technology services that focus on the social determinants of health. There is limited, vague, or outdated information on UIO websites regarding the type of cancer-related services and programs provided. We found that while twenty-one of thirty-four UIOs list any mention of cancer screenings, few mentioned specific testing capabilities for various cancers. In addition, the listing of support and preventative services was also limited with less than half of UIOs reporting on patient navigation services, among others. There is untapped potential in the utilization of websites for extending the impact of UIOs and their work with urban AI/AN populations in prevention, screening, and support of cancer patients in a culturally appropriate manner that can improve outcomes.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959787","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":"Efficacy of CBP/p300 Dual Inhibitors against Derepression of KREMEN2 in cBAF-Deficient Cancers.","authors":"Mariko Sasaki, Daiki Kato, Hiroshi Yoshida, Takafumi Shimizu, Hideaki Ogiwara","doi":"10.1158/2767-9764.CRC-24-0484","DOIUrl":"10.1158/2767-9764.CRC-24-0484","url":null,"abstract":"<p><strong>Significance: </strong>In this study, we clarified that the cBAF subcomplex is deficient in the SWI/SNF complex, resulting in dependency on the CBP/p300 paralog pair. Simultaneous inhibitors of the CBP/p300 paralog pair show promise for cBAF-deficient lung cancer, as well as rare cancers such as malignant rhabdoid tumors, epithelioid sarcomas, and synovial sarcomas.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"24-38"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775349","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":"Serially Quantifying TERT Rearrangement Breakpoints in ctDNA Enables Minimal Residual Disease Monitoring in Patients with Neuroblastoma.","authors":"Jan F Hollander, Annabell Szymansky, Jasmin Wünschel, Kathy Astrahantseff, Carolina Rosswog, Anne Thorwarth, Theresa M Thole-Kliesch, Rocío Chamorro González, Patrick Hundsdörfer, Kathrin Hauptmann, Karin Schmelz, Dennis Gürgen, Julian M M Rogasch, Anton G Henssen, Matthias Fischer, Johannes H Schulte, Cornelia Eckert, Angelika Eggert, Marco Lodrini, Hedwig E Deubzer","doi":"10.1158/2767-9764.CRC-24-0569","DOIUrl":"10.1158/2767-9764.CRC-24-0569","url":null,"abstract":"<p><strong>Significance: </strong>Real-time molecular monitoring of TERT-rearranged high-risk neuroblastoma is an unmet clinical need. We tested liquid biopsy-based assays for patient-individualized TERT breakpoint sequences to monitor disease in pediatric patients. Our digital PCR approach provides high resolution of spatial and temporal disease quantification in individual patients and is applicable for clinical routine.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"167-177"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933790","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":"Deep Learning Predicts Subtype Heterogeneity and Outcomes in Luminal A Breast Cancer Using Routinely Stained Whole-Slide Images.","authors":"Nikhil Cherian Kurian, Peter H Gann, Neeraj Kumar, Stephanie M McGregor, Ruchika Verma, Amit Sethi","doi":"10.1158/2767-9764.CRC-24-0397","DOIUrl":"10.1158/2767-9764.CRC-24-0397","url":null,"abstract":"<p><strong>Significance: </strong>A deep learning model, trained using transcriptomic data, inexpensively quantifies and fine-maps ITH due to subtype admixture in routine images of LumA breast cancer, the most favorable subtype. This new approach could facilitate exploration of the mechanisms behind such heterogeneity and its impact on selection of therapy for individual patients.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"157-166"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911229","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 Cost-Effective Two-Step Approach for Multi-Cancer Early Detection in High-Risk Populations.","authors":"Shuaipeng Geng, Shiyong Li, Wei Wu, Yinyin Chang, Mao Mao","doi":"10.1158/2767-9764.CRC-24-0508","DOIUrl":"10.1158/2767-9764.CRC-24-0508","url":null,"abstract":"<p><strong>Significance: </strong>Large-scale screening inevitably leads to significant financial burdens on the healthcare system, which is a key factor constraining nationwide screenings. The two-step MCED approach not only maintains comparable performance but also substantially alleviates financial strains compared with the direct use of next-generation sequencing-based MCED tests for massive screenings.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"150-156"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911266","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":"First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies.","authors":"Shivaani Kummar, Albiruni Abdul Razak, Scott Laurie, Dylan M Glatt, Sariah Kell, Anh N Diep, Maike Schmidt, Clifford Hom, Chris German, Suyash S Shringarpure, Sophia R Majeed, Drew Rasco","doi":"10.1158/2767-9764.CRC-24-0568","DOIUrl":"10.1158/2767-9764.CRC-24-0568","url":null,"abstract":"<p><strong>Purpose: </strong>In this phase 1 portion of a first-in-human phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.</p><p><strong>Patients and methods: </strong>Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks (Q3W) using an accelerated titration design followed by a traditional 3 + 3 design, with an initial dose level of 2 mg.</p><p><strong>Results: </strong>Twenty-eight participants were enrolled across seven cohorts and received a median of four cycles of 23ME-00610. No treatment-related serious adverse events (AE) were observed, and the maximum tolerated dose was not reached. Overall, the PK of 23ME-00610 was linear and dose proportional for doses ≥60 mg, with a median terminal half-life of 13 days at 1,400 mg. Peripheral saturation of CD200R1 was observed for doses ≥60 mg. Immune-related AEs, including rash, pruritus, and hypothyroidism, were predicted by phenome-wide association studies and observed for doses ≥60 mg. A confirmed partial response was observed in a participant with well-differentiated pancreatic neuroendocrine cancer whose tumor was among those with the highest tumor CD200 expression.</p><p><strong>Conclusions: </strong>23ME-00610 has mild-to-moderate on-target AEs and PK/PD consistent with tumor target saturation and dosing every 3 weeks. The trend for clinical benefit in participants with tumor CD200 expression suggests that 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary antitumor activity, 1,400 mg Q3W was selected as the dose for further study.</p><p><strong>Significance: </strong>Genome-wide association studies (GWAS) of the 23andMe genetic database identified CD200R1 as a promising therapeutic target for cancer. This phase 1 study of 23ME-00610, a CD200R1 antagonist IgG1, showed acceptable safety and tolerability, PK supporting Q3W dosing, and PD and preliminary clinical activity supporting an initial recommended phase 2 dose of 1,400 mg.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"94-105"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803694","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":"Acknowledgment to Reviewers.","authors":"","doi":"10.1158/2767-9764.CRC-5-1-AR","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-5-1-AR","url":null,"abstract":"","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":"5 1","pages":"1-4"},"PeriodicalIF":2.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933796","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}