Nicholas Hornstein Highlights Proteotranscriptomic Insights in MSS Early-Onset Colorectal Cancer
Nicholas Hornstein, Gastrointestinal Medical Oncologist at Northwell Health, shared a post on X about a paper by Jumanah Yousef Alshenaifi et al. published in JCO Oncology Advances:
“Despite its rising incidence and poor outcomes, we still have a limited understanding of the biology driving early-onset colorectal cancer (<50y). Most prior studies were small, inconsistent, or confounded by MSI and treatment exposure.
In JCO OA, Futreal, Scott Kopetz, and colleagues take a major step forward with an integrated proteotranscriptomic analysis – combining RNA sequencing and proteomic profiling – across two independent MSS cohorts (MD Anderson and TCGA). This design allows for a clearer view of pathway activity and protein-level validation.
Key findings:
- Wnt/β-catenin signaling – high
- EMT programs – low
- MAPK pathway hyperactive – even with/ RAS WT
- Proteomics confirms high RAF, HER2, mTOR
Takeaway: EOCRC is biologically distinct, with MAPK activation independent of KRAS mutations. That creates an opening for MAPK-directed strategies in a population where conventional therapy often falls short.
Congrats to Drs. Futreal, Kopetz, and team on this important advance in EOCRC biology.”
Title: Proteotranscriptomic Analyses of Microsatellite-Stable Early-Onset Colorectal Cancer
Authors: Jumanah Yousef Alshenaifi, Giulia Maddalena, Jessica C. Lal, Oluwadara Coker, Hey Min Lee, Oscar Eduardo Villarreal, Ganiraju Manyam, Alaa M. Mohamed, Guglielmo Vetere, Micheal White, Nadim Ajami, Preeti Kanikarla Marie, Alexey Sorokin, David Menter, Y. Nancy You, Andy Futreal, Scott Kopetz
You can read the Full Article on JCO Oncology Advances.
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