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    Drug Sensitivities in Colorectal Cancer Peritoneal Metastases

    Publication Title: Consensus Molecular Subtypes Inform HIPEC Agent Selection in Colorectal Cancer Peritoneal Metastases

    Summary

    Question
    This study explored whether colorectal cancer with peritoneal metastases (CRC-PM), a form of advanced cancer that spreads to the lining of the abdominal cavity, shows distinct responses to hyperthermic intraperitoneal chemotherapy (HIPEC) agents based on consensus molecular subtypes (CMS). Specifically, the researchers aimed to identify drug sensitivity patterns in CRC-PM to improve HIPEC agent selection.
    Why it Matters
    CRC-PM is challenging to treat, and HIPEC, which involves delivering heated chemotherapy directly into the abdominal cavity during surgery, offers promise. However, its effectiveness varies among patients. Identifying how molecular subtypes of CRC-PM respond to specific drugs could allow for personalized treatment strategies, improving patient outcomes and potentially reducing side effects. This research has significance for clinicians treating advanced colorectal cancer and patients seeking better-targeted therapies.
    Methods
    The researchers analyzed drug sensitivity data from 34 colorectal cancer cell lines categorized into four consensus molecular subtypes: CMS1, CMS2, CMS3, and CMS4. They tested five commonly used HIPEC agents—mitomycin-C, oxaliplatin, irinotecan, 5-fluorouracil, and cisplatin—using a database that measures how well drugs inhibit cancer cell growth. Sensitivity was assessed based on changes in cell viability, expressed as log2 fold change.
    Key Findings
    The researchers found that CMS4 cell lines, which are often associated with aggressive cancer behavior, were more sensitive to mitomycin-C compared to CMS2. Additionally, CMS4 and CMS3 cell lines showed higher sensitivity to irinotecan than CMS1 and CMS2. However, oxaliplatin, 5-fluorouracil, and cisplatin did not demonstrate significant differences in sensitivity across subtypes. These results highlight distinct drug sensitivity patterns for CMS4, suggesting that mitomycin-C and irinotecan may be more effective for HIPEC in patients with this subtype.
    Implications
    The findings suggest that molecular subtyping of CRC-PM could guide the selection of HIPEC agents, improving treatment outcomes for patients. Specifically, CMS4 patients may benefit from personalized HIPEC strategies using mitomycin-C or irinotecan, while the limited efficacy of oxaliplatin highlights the need for tailored approaches. This research advances the understanding of how molecular characteristics impact chemotherapy effectiveness in advanced colorectal cancer.
    Next Steps
    The authors recommend further clinical trials to validate these findings by integrating genomic subtyping and drug sensitivity testing into HIPEC protocols. This could establish personalized treatment strategies for CRC-PM, ultimately improving patient outcomes and advancing precision oncology.
    Funding Information
    This research was supported by the National Institutes of Health (awards P30CA016359 and S10OD026996). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Yale University also provided funding and support for this research.

    Full Citation

    Gupta P, Godfrey E, Schultz K, Qiao L, Aguirre N, Bader J, Foote M, Shen J, Shergill A, Cecchini M, Sundar R, Sheltzer J, Turaga K. Consensus Molecular Subtypes Inform HIPEC Agent Selection in Colorectal Cancer Peritoneal Metastases. Annals Of Surgical Oncology 2026, 1-6. PMID: 41634518, DOI: 10.1245/s10434-025-19057-z.

    Authors

    • Princy Gupta

      First Author
      School Building Streamline Icon: https://streamlinehq.comOther Institution

    • Kiran Turaga, MD, MPH

      Last Author
      Yale School of Medicine

      Professor of Surgery (Oncology)

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    Additional Yale School of Medicine Authors

    Other Authors

    • Lu Qiao;
    • Nicole Aguirre;
    • Justin M. Bader;
    • Michael B. Foote;
    • John Paul Shen;
    • Ardaman P. Shergill;
    • Raghav Sundar;
    • Jason M. Sheltzer

    Research Themes

    Concepts