Advantages:
- Novel biomarker development: Unique 10-gene signatures distinguish the contributions of tumor epithelium (EPI) & tumor microenvironment (TME) in colorectal cancer (CRC)
- Clinical Relevance: EPIS signature predicts better progression-free survival in cetuximab-treated metastatic CRC patients; TMES correlates with worse survival outcomes
- Enhanced predictive value for targeted/personalized therapy
Summary:
Colorectal cancer (CRC) is a heterogeneous disease marked by significant variability in outcomes and therapy responses, largely due to the complex interplay between tumor epithelium (EPI) and tumor microenvironment (TME). tumor cells and surrounding immune and stromal components. Disentangling these different contributors remains challenging for clinicians and researchers alike. Current approaches have struggled to clearly delineate how specific features within the microenvironment drive resistance or sensitivity to targeted therapies.
Our researchers have developed two distinct 10-gene signatures, TMES (TME-associated) and EPIS (EPI-associated), to: a) distinguish the distinct tumor microenvironment (TME) and tumor epithelium (EPI); b) to predict CRC progression and therapeutic response to therapy. The researchers classified 2373 CRC tumors into CMS1-4 subtypes and derived the TMES and EPIS signatures from a highly prognostic 500-gene signature. The signatures were validated using CIBERSORT deconvolution and single-cell RNA sequencing (scRNASEQ). Results indicate that the TMES signature is associated with immune/stromal-rich CMS1/CMS4 subtypes, which portend worse survival, while the EPIS signature is linked to epithelial CMS2/CMS3 subtypes, which portend better survival.
Medico 150 CRC cell lines treated with 10 μg/mL cetuximab, categorized by the 10-gene EPI (NEG), showed more than 75% growth inhibition in WT KRAS/BRAF cell lines.
Desired Partnerships:
- License
- Sponsored Research
- Co-Development