In mice with human tumors carrying common RAS mutations, a lab-made protein called JAM20 shrinks tumors by turning down the activity of ERK, a protein that drives cancer 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 ERK suppression via Switch I/II pocket inhibition consistently correlates with tumor regression across RAS-mutant cancers in preclinical and clinical settings.
A systematic review and meta-analysis of all published studies measuring pERK suppression and tumor volume change in RAS-mutant xenografts treated with Switch I/II inhibitors, correlating biomarker reduction with efficacy.
Whether a Switch I/II inhibitor that suppresses pERK improves survival compared to a non-ERK-suppressing agent in patients with RAS-mutant cancers.
A double-blind RCT of 300 patients with advanced RAS-mutant cancers, randomized to a Switch I/II inhibitor (expected to suppress pERK) versus a MEK inhibitor (also suppresses pERK) or placebo, with pERK as a pharmacodynamic biomarker and overall survival as primary endpoint.
Whether the degree of pERK suppression in tumors predicts clinical response to Switch I/II inhibitors.
A prospective cohort of 180 patients with RAS-mutant cancers treated with a Switch I/II inhibitor, measuring tumor pERK levels pre- and post-treatment via biopsy and correlating with tumor response and progression-free survival.
Whether non-responders to Switch I/II inhibitors show less pERK suppression than responders.
A case-control study comparing 40 responders to a Switch I/II inhibitor with 80 non-responders, measuring baseline and on-treatment pERK levels in tumor biopsies to determine if suppression magnitude differs.
The baseline level of pERK in tumors with different RAS mutations.
A cross-sectional analysis of 300 tumor samples from patients with KRAS(G12D), KRAS(G12V), HRAS(Q61L), or NRAS(Q61K) mutations, measuring pERK levels via immunohistochemistry to compare baseline MAPK activation across mutation types.