RCSI study identifies new treatment targets for most common type of colorectal cancer

An international study led by RCSI University of Medicine and Health Sciences and The Institute of Cancer Research, London, has identified new treatment targets for microsatellite-stable (MSS) colorectal cancer, which accounts for 80% to 85% of Ireland's 2,500 annual cases. Using the AI tool iPhenMap on 2,000 tumor samples, researchers discovered vulnerabilities and demonstrated that repurposing approved drugs like trametinib significantly reduced tumor growth in laboratory models.

Development and findings of iPhenMap

• ▪Multiomic analysis of 2,000 tumor samples exposed previously unrecognized ways in which microsatellite-stable colorectal cancer cells divide, grow, adapt, and interact with their biological environment.
• ▪An international research team led by RCSI University of Medicine and Health Sciences and The Institute of Cancer Research, London, developed an artificial intelligence tool called iPhenMap to create biological maps of tumors.
• ▪Biological tumor mapping using iPhenMap revealed previously unidentified connections between genetic and metabolic features in microsatellite-stable colorectal cancer.
• ▪The iPhenMap artificial intelligence tool integrated genetic, metabolic, protein, epigenetic, single-cell, and clinical data from 2,000 patient tumor samples to uncover hidden cellular mechanisms.

Repurposing trametinib for colorectal cancer

• ▪Trametinib is an existing targeted cancer therapy approved to treat melanoma, lung cancer, and thyroid cancer presenting specific genetic mutations.
• ▪In laboratory models of microsatellite-stable colorectal cancer, combining the targeted drug trametinib with other medications significantly reduced tumor growth and extended survival.
• ▪The RCSI-led study provides a roadmap for repurposing existing approved medications to establish personalized treatments for microsatellite-stable colorectal cancer patients.

STC-1010 immunotherapy trial results

• ▪Treatment with STC-1010 enabled 43% of initially unresectable metastatic colorectal cancer patients in the BreAK CRC-001 trial to become eligible for surgical resection.
• ▪The STC-1010 immunotherapy regimen nearly quadrupled cytotoxic CD8+ T-cell infiltration inside microsatellite-stable colorectal tumors by 285% compared to baseline levels.
• ▪In the Phase Ia BreAK CRC-001 trial, Brenus Pharma's immunotherapy STC-1010 achieved 100% disease control and a 57% objective response rate among seven evaluable microsatellite-stable colorectal cancer patients.

Microsatellite-stable colorectal cancer background

• ▪Microsatellite-stable colorectal cancer tumors historically respond poorly to newer targeted therapies, immunotherapies, and combination chemotherapy trials.
• ▪Microsatellite-stable colorectal cancer accounts for 80% to 85% of the 2,500 new colorectal cancer cases diagnosed annually in Ireland.