A lab-designed protein called JAM20 attaches to a specific region on mutated RAS proteins found in many cancers, blocking signals that drive tumor growth and shrinking tumors in mice, which shows this region can be targeted to stop cancer progression.
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 targeting the RAS Switch I/II pocket with any therapeutic agent (small molecule or biologic) consistently improves survival or tumor response across multiple RAS-mutant cancer types in humans.
A systematic review and meta-analysis of all published randomized controlled trials evaluating Switch I/II pocket inhibitors (e.g., BI-2852 derivatives, JAM20-like biologics) in patients with advanced KRAS, HRAS, or NRAS-mutant solid tumors, measuring overall survival, progression-free survival, and objective response rate as primary endpoints.
Whether a Switch I/II pocket-targeting drug (e.g., JAM20 delivered via lipid nanoparticles) improves survival or tumor control compared to standard therapy in patients with RAS-mutant cancers.
A double-blind, placebo-controlled phase III trial of 400+ patients with advanced KRAS(G12D/V), HRAS(Q61L), or NRAS(Q61K) mutant cancers, randomized to receive intravenous JAM20-like biologic (delivered via lipid nanoparticles, 5 mg/kg weekly) plus standard care versus standard care alone, with overall survival as the primary endpoint and tumor response by RECIST 1.1 as secondary.
Whether patients with RAS-mutant tumors expressing high levels of Switch I/II pocket accessibility biomarkers have better outcomes when treated with inhibitors targeting this region.
A prospective multicenter cohort study of 300 patients with RAS-mutant cancers undergoing treatment with Switch I/II pocket inhibitors, tracking tumor molecular profiles (e.g., RAS conformational state, pocket accessibility via PET probes), treatment response, and survival over 24 months.
Whether patients who respond to Switch I/II pocket inhibitors have distinct RAS mutation subtypes or co-mutations compared to non-responders.
A case-control study comparing 50 patients with RAS-mutant cancers who achieved partial response to a Switch I/II inhibitor with 100 non-responders, analyzing tumor genomic profiles for co-mutations (e.g., TP53, STK11), RAS isoform, and nucleotide state prevalence.
The prevalence of RAS mutations with structural features enabling Switch I/II pocket binding in a population of cancer patients.
A cross-sectional analysis of 500 tumor samples from patients with pancreatic, lung, or colorectal cancers, using structural modeling and sequencing to determine the proportion of RAS mutations (KRAS/G12D, HRAS/Q61L, NRAS/Q61K) that preserve the Switch I/II pocket conformation.