Cancer research communications最新文献

{"title":"Development and Application of MiMouse, a Comprehensive Genomic Profiling Panel for Credentialling Mouse Tumor Models.","authors":"Kevin Hu, Chia-Jen Liu, Zhaoping Qin, Aaron M Udager, Marcin P Cieslik, Scott A Tomlins","doi":"10.1158/2767-9764.CRC-25-0279","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-25-0279","url":null,"abstract":"<p><p>Despite shared genetic driver alterations and histology, the genomic fidelity of most mouse tumor models, including those genetically engineered (GEMM), to their human counterparts is unknown. Here, we developed MiMouse, a mouse comprehensive genomic profiling panel for high throughput credentialling applicable to routine FFPE tumors. Through simulation/validation, we focused on considerations for cross-species mutation prioritization, strain determination, and aneuploidy detection. Using MiMouse, we profiled >250 tumors from high-grade serous carcinoma (HGSC) GEMMs based on conditional inactivation of Brca1 (B), Trp53 (P), Pten (Pt), Rb1 (R), and/or Nf1 (N), and a colorectal carcinoma (CRC) GEMM based on conditional inactivation of Apc, Kras and/or P. We confirmed increased genomic instability in HGSC tumors, with BPPt cancers having both the shortest latency and the least genomic instability. In CRC, focusing on fidelity to human CRC aneuploidy events, our results highlighted the critical importance of synteny in transgenic studies, as not only was loss of mouse chromosome 18 (containing the tumor suppressor gene Smad4) a significant aneuploidy event (18%), additional tumors harbored focal Smad4 copy loss, potentially due to the mouse-specific proximity of Apc (mouse and human chromosomes 18 and 5, respectively). Likewise, mouse chromosome 5, the only significantly gained (46%) chromosome in our CRC models, has syntenic blocks from human chromosomes 7p, 7q and 13q, including Cdx2, which is both a lineage specific CRC oncogene and the CRC GEMM promoter source. Given the importance of mice to translational cancer research, this study highlights the considerations and utility of approaches for comprehensive genomic credentialling.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240424","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":"Multiplexed imaging mass cytometry reveals tumor-immune microenvironment-dependent hormone receptor expression in adult type ovarian granulosa cell tumors.","authors":"Eleonora Y Khlebus, Veena K Vuttaradhi, Sammy Ferri-Borgogno, Allison L Brodsky, Barrett C Lawson, Samuel C Mok, R Tyler Hillman","doi":"10.1158/2767-9764.CRC-25-0333","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-25-0333","url":null,"abstract":"<p><p>Adult-type granulosa cell tumors (AGCTs) are rare ovarian tumors with few effective treatments for recurrent disease. To elucidate spatial features and cellular interactions within the AGCT tumor microenvironment (TME), we applied imaging mass cytometry (IMC) using a 34-marker panel on 130 regions from 24 AGCT samples, profiling over 900,000 single cells. Analysis confirmed the immune \"cold\" phenotype of AGCTs and showed higher macrophage abundance in recurrent compared to primary tumors. We observed substantial heterogeneity in tissue architecture across samples, including variable presence of FOXL2+ cells embedded in collagen-rich regions (FOXL2+COL1A1+ cells). Based on TME composition, we defined two AGCT subtypes: AGCT-1 and AGCT-2 with distinct FOXL2+ cell distributions, differences in progesterone receptor (PR) expression, and unique transcriptomic profiles. Our findings highlight the role of macrophages, Foxl2+ subpopulations, and extracellular matrix (ECM) in AGCT progression and suggest AGCT subtype-specific vulnerabilities that could inform personalized therapies for this rare malignancy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214095","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":"RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.","authors":"Zahra Davoudi, Thomas S Dexheimer, Nathan P Coussens, Thomas Silvers, Raymond G Fox, Samantha B Kemp, Poorva Juneja, Joel Morris, Melinda G Hollingshead, Naoko Takebe, James H Doroshow, Beverly A Teicher","doi":"10.1158/2767-9764.CRC-24-0582","DOIUrl":"10.1158/2767-9764.CRC-24-0582","url":null,"abstract":"<p><p>The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is among the most frequently altered genes in cancer, and the KRAS protein was long deemed undruggable. Recent strategies to target oncogenic KRAS have included both direct inhibition of the KRAS protein and indirect inhibition of its activity by targeting upstream and downstream signaling pathway mediators. A high-throughput screen of multicell-type tumor spheroids was designed to identify active combinations of targeted small molecules and KRAS pathway inhibitors. Inhibitors of the nonreceptor protein tyrosine phosphatase Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) and the guanine nucleotide exchange factor Son of Sevenless homolog 1 (SOS1) were tested to evaluate indirect upstream pathway inhibition, whereas sotorasib directly inhibited the KRAS G12C variant. As single agents, sotorasib and the SHP2 inhibitor batoprotafib (TNO155) exhibited selectivity toward spheroids with KRAS G12C, whereas the SOS1 inhibitor BI-3406 showed varying activity across KRAS variants. Vertical inhibition of the rat sarcoma virus (RAS)/MEK/ERK pathway by targeting SHP2 or SOS1 and the downstream kinases MEK (trametinib) or ERK (temuterkib) was highly effective. Inhibition of upstream tyrosine receptor kinases with nintedanib in combination with batoprotafib or BI-3406 was also effective and, in combination with sotorasib, demonstrated synergy in spheroids harboring KRAS G12C. Dual inhibition of the RAS/MEK/ERK and PI3K/Ak strain transforming (AKT)/mTOR pathways by batoprotafib or sotorasib with either the mTORC1/2 inhibitor sapanisertib or the AKT inhibitor ipatasertib demonstrated combination activity, primarily in spheroids harboring KRAS G12C. The BCL-2 inhibitor venetoclax, in combination with sotorasib, batoprotafib, or BI-3406, resulted in additive and synergistic cytotoxicity. Lastly, concurrent inhibition of the KRAS pathway with sotorasib and batoprotafib demonstrated combination activity in spheroids containing KRAS G12C.</p><p><strong>Significance: </strong>KRAS variants are oncogenic drivers for a range of human cancers. Multiple combinations of small-molecule agents that target RAS signaling were screened and reduced the viability of multicell-type tumor spheroids from a variety of human solid tumors. Combinations warranting further testing were identified.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1779-1795"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076588","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":"Immune Activation Signatures Associated with Fatigue in Cancer Patients Undergoing Immune Checkpoint Inhibitor Therapy.","authors":"Howard L Li, Soren Charmsaz, Mari Nakazawa, Stephanie L Alden, Madelena Brancati, James M Leatherman, Ervin Griffin, Hua-Ling Tsai, Nicole E Gross, Christopher J Thoburn, Alexei Hernandez, Erin M Coyne, Sarah M Shin, Royce P Lee, Evan J Lipson, Burles A Johnson, Aliyah Pabani, Yasser Ged, Marina Baretti, Julie R Brahmer, Jean Hoffman-Censits, Tanguy Y Seiwert, Daniel J Zabransky, Jennifer N Durham, Elizabeth M Jaffee, G Scott Chandler, Brittany L Adler, Won Jin Ho, Chester Kao, Mark Yarchoan","doi":"10.1158/2767-9764.CRC-25-0240","DOIUrl":"10.1158/2767-9764.CRC-25-0240","url":null,"abstract":"<p><p>Fatigue is a common and often debilitating adverse event among patients receiving immune checkpoint inhibitor (ICI) therapy, yet its underlying immunologic mechanisms remain poorly defined. We prospectively collected clinical data and blood samples from patients with solid tumors receiving ICI therapy. Patients were prospectively surveyed at month 2, 4, or 6 on treatment to assess for the presence and severity of fatigue as compared with treatment baseline. We analyzed peripheral lymphocyte populations by cytometry by time of flight and peripheral levels of 39 cytokines with a Luminex multiplex assay to identify dynamic immune changes associated with ICI-related fatigue. Of 53 patients enrolled, 31 (58.5%) reported worsening fatigue during ICI therapy. Patients reporting fatigue exhibited broad early-treatment elevations in circulating cytokines, with the most prominent increases observed in the Th1-associated cytokine cluster, including IFN-γ, IL-2, and IL-12. In parallel, several clusters of cytotoxic effector CD8+ T cells expanded significantly from baseline in the fatigued group. Fatigue was not associated with objective tumor response or with the development of other clinically meaningful immune-related adverse events. In a pan-tumor cohort treated with ICIs, increases in clusters of cytotoxic effector CD8+ T cells in parallel with related Th1-associated cytokines were associated with ICI-related fatigue, implicating fatigue as a potential marker of immune activation in this population.</p><p><strong>Significance: </strong>This study illuminates dynamic changes in peripheral cytokines and immune cell clusters that are associated with ICI-related fatigue. Namely, this study implicates the Th1 pathway as a novel contributor to ICI-related fatigue and identifies ICI-related fatigue as a clinical surrogate for immune activation in patients receiving ICI therapy. Recognizing that fatigue may be a biomarker of heightened immune activity influences monitoring strategies and informs supportive care interventions during immunotherapy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1738-1746"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066590","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":"Novel Afro-Caribbean Prostate Cancer Model Reveals Ancestry-Specific Drug Vulnerabilities with Therapeutic Implications for Black Patients.","authors":"Simone Badal, Bor-Jang Hwang, Ashlianne Nelson, Kristoff Frank, Tanisha Maitre, Magdalene Nwokocha, Rory Thompson, Belinda Morison, Rajini Haraksingh, Valerie Odero-Marah, Camille Ragin","doi":"10.1158/2767-9764.CRC-25-0254","DOIUrl":"10.1158/2767-9764.CRC-25-0254","url":null,"abstract":"<p><p>In the era of targeted therapeutics, the inadequate representation of Black populations in prostate cancer models limits effective drug screening. In this study, we introduce ACRJ-PC28, a novel Afro-Caribbean prostate cancer cell line, and evaluate its responses to five anticancer drugs (docetaxel, cabazitaxel, abiraterone, olaparib, and enzalutamide) and betaine. We compare these responses with those of established prostate cancer cell lines from Black (MDA-PCA-2b) and White (DU-145 and PC-3) donors using three distinct viability assays. We observed ancestry-dependent drug sensitivities: abiraterone showed remarkable selectivity for ACRJ-PC28 (IC50 = 1.10 μmol/L), being 4.6- to 13.1-fold more potent than in other cell lines, whereas enzalutamide demonstrated pronounced racial differences, being 3 to 5 times less effective in cell lines from Black donors (IC50 = 206 μmol/L for ACRJ-PC28; 104 μmol/L for MDA-PCA-2b) versus cell lines from White donors (IC50 = 37 μmol/L for PC-3; 48 μmol/L for DU-145). RNA sequencing analysis revealed consistent underexpression of TNF family genes, particularly TNFRSF14, in prostate cancer cells from Black donors correlating with differential drug responses. Despite underexpressing AR, the ACRJ-PC28 line exhibited exceptional sensitivity to abiraterone, consistent with clinical observations that Black patients with prostate cancer respond better to this therapy. This aligns with its neuroendocrine phenotype in the source patient, who succumbed within 1 year despite androgen deprivation therapy. Our findings suggest that incorporating diverse prostate cancer models in preclinical screening could guide personalized treatment strategies for Black patients who experience disproportionate prostate cancer mortality by identifying ancestry-specific drug vulnerabilities that inform optimal therapeutic combinations.</p><p><strong>Significance: </strong>This study introduces ACRJ-PC28, the first Afro-Caribbean prostate cancer cell line, revealing ancestry-dependent drug sensitivities that could explain differential clinical outcomes. The findings demonstrate critical gaps in current preclinical models and support incorporating diverse cell lines to develop personalized treatment strategies for underrepresented populations experiencing disproportionate cancer mortality.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":"5 10","pages":"1758-1770"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214091","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 Analysis of Rare RAS Variants of Unknown Significance.","authors":"Soohwan Park, Masachika Ikegami, Rina Kitada, Kazuya Takamochi, Kenji Suzuki, Hiroyuki Mano, Shinji Kohsaka","doi":"10.1158/2767-9764.CRC-25-0188","DOIUrl":"10.1158/2767-9764.CRC-25-0188","url":null,"abstract":"<p><p>The RAS gene is frequently mutated in human cancers. Whereas the functional significance of frequent mutations is well established, the significance of rare mutations remains unknown. This study aimed to comprehensively investigate the function of rare RAS variants and provide new insights about their clinical relevance. A total of 298 K/N/HRAS variants (169, 72, and 57 variants, respectively) reported in the COSMIC database v100 were introduced into 3T3 cells. Subsequently, the drug sensitivity of KRAS variants to BI-2865, a noncovalent pan-KRAS inhibitor, was evaluated using the mixed-all-nominated-in-one method. The 3T3 focus formation assay newly identified 35 KRAS, 10 NRAS, and 21 HRAS variants as transforming competent. The oncogenicity assessed in the present study was consistent with that reported in the database. The drug sensitivity assay identified 15 KRAS variants sensitive to BI-2865. BI-2865 treatment inhibited the RAS downstream signaling pathways and induced apoptosis in cells with the sensitive variants. The present study identified 66 new oncogenic RAS variants. The sensitivity of KRAS variants to BI-2865 varies by variant. Functional analysis provides clues for the treatment of patients with rare RAS variants.</p><p><strong>Significance: </strong>This study presents the first comprehensive functional analysis of 298 rare RAS variants, identifying 66 novel oncogenic mutations and 15 KRAS variants sensitive to the noncovalent pan-KRAS inhibitor BI-2865. The heterogeneity in drug responses among KRAS variants underscores the need for variant-specific therapeutic strategies. These findings provide a preclinical framework for guiding personalized treatment in RAS-driven cancers and a valuable resource for understanding the clinical relevance of rare RAS mutations.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1747-1757"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12488390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088442","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 First-In-Human Dose-Escalation Phase I Study of Basroparib, a Tankyrase Inhibitor, in Patients with Advanced-Stage Solid Tumors.","authors":"Christopher H Lieu, Heinz-Josef Lenz, Al B Benson, Xue Meng, Uk-Il Kim, Song Hyun Kim, Kyungjin Kim, Moo Je Sung","doi":"10.1158/2767-9764.CRC-25-0502","DOIUrl":"10.1158/2767-9764.CRC-25-0502","url":null,"abstract":"<p><strong>Purpose: </strong>The pathogenesis of colorectal cancer is largely driven by mutations of the tumor suppressor gene APC (adenomatous polyposis coli) that lead to aberrant activation of the β-catenin-dependent (canonical) Wnt signaling pathway. We evaluated basroparib, a tankyrase-selective inhibitor targeting the Wnt/β-catenin signaling pathway, in a first-in-human phase I clinical study for safety, tolerability, pharmacokinetics, and efficacy in patients with advance-stage solid tumors.</p><p><strong>Patients and methods: </strong>Patients enrolled to this open-label, multicenter study (NCT04505839) were treated with basroparib capsules orally once daily in 28-day cycles (21-day on and 7-day off) in dose escalation at seven dose levels (30-360 mg) following the classic \"3 + 3\" design.</p><p><strong>Results: </strong>Twenty-five patients (colorectal cancer, 23 patients; male sex, 48%, and median age, 58 years) were treated with basroparib. Dose-limiting toxicities and fatal treatment-related adverse events were not observed. The most commonly reported treatment-related adverse events were fatigue and nausea with mild/moderate severity. Basroparib pharmacokinetics increased less than proportionally with dose increase up to 300 mg. Among 17 patients evaluated for response, four (23.5%) had stable disease with a duration of up to 2.5 months and relative higher drug exposure compared with others. The dose of 360 mg was determined to be the maximum tolerated dose and recommended phase II dose.</p><p><strong>Conclusions: </strong>Basroparib was shown to be a safe and well-tolerated tankyrase-selective inhibitor with preliminary antitumor activity warranting further investigation.</p><p><strong>Significance: </strong>Tankyrase in the active β-catenin-dependent (canonical) Wnt signaling pathway has been a desirable but difficult target because of safety concerns. We developed a tankyrase-selective inhibitor, basroparib, and successfully introduced it in a first-in-human study. This study demonstrated a favorable safety profile and modest antitumor activity for basroparib and suggests that basroparib may play a role when combined with other rational targeted therapies.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":"1771-1778"},"PeriodicalIF":3.3,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082545","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":"Mapping the Proteomic Landscape of Pancreatic Cancer: Prognostic Insights and Subtype Stratification.","authors":"Adel T Aref, Jason Grealey, Mohashin Pathan, Zainab Noor, Asim Anees, Akm Azad, Daniela Lee Smith, Erin M Humphries, Daniel Bucio-Noble, Jennifer Ms Koh, Erin Sykes, Steven G Williams, Ruth J Lyons, Natasha Lucas, Dylan Xavier, Sumit Sahni, Anubhav Mittal, Jaswinder S Samra, John V Pearson, Nicola Waddell, Olga Kondrashova, Angela Chou, Loretta Sioson, Amy Sheen, Australian Pancreatic Cancer Genome Initiative Apgi, Peter G Hains, Phillip J Robinson, Qing Zhong, Roger R Reddel, Anthony J Gill","doi":"10.1158/2767-9764.CRC-25-0229","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-25-0229","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy that lacks reliable biomarkers to guide treatment decisions. Effective prognostic tools are needed to improve its clinical management. We conducted a comprehensive proteomic analysis on 115 PDA patient samples with matched adjacent normal tissue. Differential abundance and pathway analyses identified upregulated proteins and pathways within key subgroups. Unsupervised consensus clustering was used to establish a proteomic-based classification of PDA subtypes. A protein-based risk score was developed and validated using multicox regression analyses with LASSO regularization. A 20-protein diagnostic panel was identified (LGALS1, ANXA2, LGALS3BP, CTSD, S100P, COL12A1, SFN, THBS2, CTHRC1, THBS1, SERPINB5, LAMC2, POSTN, CEACAM6, CTSE, PLEC, PKM, S100A11, TAGLN2, ALDOA). Consensus clustering analysis identified four prognostic proteomic subtypes. Subtypes with poorer prognoses exhibited upregulation of neutrophil degranulation, extracellular matrix remodeling, focal adhesion, Mesenchymal Epithelial Transition, collagen formation, and PI3K-Akt-mTOR-related pathways, indicating a predominance of basal-like and activated stromal features. In tumors with Homologous Recombination Deficiency or COSMIC Signature-3, several immune-related proteins were enriched. An 18-protein (PURB, SDCBP2, CD2BP2, GALM, SERPINA3, OAS3, FAN1, ZPR1, KRT2, NUDT2, SMNDC1, SERPINA4, CUTA, WDR36, POSTN, CLEC11A, PEX14, and PI4KA) risk score demonstrated independent prognostic significance for overall survival, and recurrence, and was validated in an independent proteomic dataset generated using a different proteomic technology. This study introduces four novel prognostic PDA subtypes and an 18-protein risk score, validated in an independent dataset, which show promise for improving survival prediction and could serve as a valuable tool for personalized treatment guidance.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151938","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":"Initial-Care Medical and Prescription Costs for Incident Metastatic versus Non-Metastatic Colorectal Cancer.","authors":"Chi M Nguyen, Paul G Yeh, Mai P Nguyen, Travis S Johnson, Hyunwoo Koo, Victoria L Champion, Todd C Skaar, David R Lairson, Patrick O Monahan, Thomas F Imperiale, Hongmei Nan","doi":"10.1158/2767-9764.CRC-25-0367","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-25-0367","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a leading cause of cancer-related death and among the costliest cancers to treat in the United States. As advanced-stage diagnoses rise, the initial-care cost differences between metastatic (mCRC) and non-metastatic CRC (non-mCRC) remain unclear, limiting insight into the financial impact of metastasis and late detection. Using Optum's de-identified Clinformatics® Data Mart, the largest U.S. commercial claims database, we examined first-year costs of care for patients aged ≥45 newly diagnosed with CRC between 2017 and 2023, with at least one year of medical records before and after diagnosis. Multivariate linear mixed-effects models estimated the impact of metastasis on medical and prescription charges and out-of-pocket (OOP) expenses (2023 USD) in relation to treatment components, emergency department (ED) visits, hospitalizations, and hospice care. Among 25,169 patients, 32.8% had metastasis at diagnosis. Treatment and care utilization were consistently higher for mCRC patients, with the greatest disparity in pharmacotherapy use (79.1% vs. 26.9%), followed by ED visits (65.4% vs. 48.1%), hospitalizations (91.1% vs. 84.0%), radiation therapy, and hospice care. Medical and prescription charges for mCRC patients ($353,255 and $5,745) were nearly double those for non-mCRC ($182,000 and $2,406), as were OOP expenses ($4,032 vs. $2,144 for medical; $319 vs. $188 for prescriptions). Pharmacotherapy was the primary cost driver in mCRC, followed by hospitalizations and ED visits. Initial-care medical and prescription costs were substantially higher for mCRC patients. These findings underscore the economic burden of metastasis, highlighting potential benefits and cost savings of early detection and intervention strategies such as routine screening.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151974","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 and safety of nivolumab monotherapy in patients with high PD-1 positive CD8/Treg ratio in advanced NSCLC and GC: A phase II, multicenter study.","authors":"Kohei Shitara, Motohiro Tamiya, Kyoichi Okishio, Hisashi Hosaka, Katsunori Shinozaki, Nobuhiko Seki, Hiroki Hara, Yukiya Narita, Takeshi Shiraishi, Yosuke Tamura, Akihito Tsuji, Kunihiro Tsuji, Naohiro Watanabe, Hiroshi Tanaka, Toshifumi Yamaguchi, Kensei Yamaguchi, Hiroki Izumi, Yasunori Ushida, Hideaki Suna","doi":"10.1158/2767-9764.CRC-25-0169","DOIUrl":"https://doi.org/10.1158/2767-9764.CRC-25-0169","url":null,"abstract":"<p><p>Background It is challenging to identify the appropriate patients who benefit from anti-PD-1/PD-L1 monotherapy. For predicting effectiveness of anti-PD-1/PD-L1 monotherapy, this open-label phase Ⅱ study (ONO-4538-88) evaluated the potential of the tumor infiltrating lymphocytes (TIL) biomarker: the balance between cytotoxic T cells and regulatory T cells. Methods Patients with advanced non-small cell lung cancer (NSCLC) or gastric cancer (GC) were screened between March 2021 and January 2022. Eligible patients who met the prespecified TIL biomarker criteria received nivolumab monotherapy. The primary endpoint was objective response rate (ORR). The secondary endpoints included overall survival (OS) and progression-free survival (PFS). Conventional biomarkers (tumor proportion score, combined positive score, tumor mutation burden, and microsatellite instability) were exploratorily analyzed, and safety was also assessed. Results Thirty-seven patients with NSCLC and 127 patients with GC were eligible for TIL analysis: 6 (16.2%) and 15 patients (11.8%) met the TIL biomarker criteria, respectively; a part of them were assessed. For NSCLC and GC, the ORR was 80.0% (4/5 patients) and 36.4% (4/11 patients), respectively; all the 5 patients and 5/11 patients had a reduction in tumor size, respectively; the median OS was not reached and 25.00 months, respectively; and the median PFS was not reached and 5.59 months, respectively. Treatment-related adverse events (TRAEs) occurred in 13/19 patients overall: 5/6 patients for NSCLC and 8/13 patients for GC. Conclusions Although the low positive rate of the TIL biomarker limits interpretation, the promising ORRs suggest the signs of the TIL biomarker's predictability for the nivolumab monotherapy.</p>","PeriodicalId":72516,"journal":{"name":"Cancer research communications","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151988","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}