JAM20 blocks cancer signals by physically occupying the same spot on RAS that the RAF protein needs to bind, stopping the signal cascade that drives uncontrolled cell growth.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether disrupting the RAS-RAF interaction via Switch I/II pocket binding consistently suppresses MAPK signaling and improves outcomes across RAS-mutant cancers.
A systematic review and meta-analysis of all published studies evaluating RAS-RAF disruption via Switch I/II pocket inhibitors, measuring MAPK pathway suppression (pERK reduction) and clinical outcomes in RAS-mutant cancers.
Whether a Switch I/II pocket inhibitor that blocks RAS-RAF binding improves survival compared to a MEK inhibitor in patients with RAS-mutant cancers.
A double-blind RCT of 300 patients with advanced KRAS-mutant cancers, randomized to receive a Switch I/II-targeting biologic (blocking RAS-RAF) versus a MEK inhibitor (trametinib), with pERK suppression as a pharmacodynamic biomarker and overall survival as primary endpoint.
Whether tumors with high RAS-RAF interaction strength show greater sensitivity to Switch I/II pocket inhibitors.
A prospective cohort of 150 patients with RAS-mutant cancers treated with a Switch I/II inhibitor, measuring RAS-RAF binding affinity in tumor lysates via co-IP and correlating with pERK suppression and clinical response.
Whether patients whose tumors retain RAS-RAF binding capability after treatment are less likely to respond to Switch I/II inhibitors.
A case-control study comparing 40 responders to a Switch I/II inhibitor with 80 non-responders, analyzing pre- and post-treatment tumor samples for RAS-RAF complex formation via co-immunoprecipitation.
The prevalence of RAS mutations that maintain high-affinity RAF binding in a population of cancer patients.
A cross-sectional analysis of 400 tumor samples from RAS-mutant cancers, measuring RAS-RAF binding affinity via co-IP and correlating with mutation type and RAS nucleotide state.