ArticleCancer discovery2024
Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05379985 (A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS), which is not on this map. Cited by 213 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS
Who cites it
213 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review.Frontiers in immunology · 2025Pooled it
- Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib guides rational combination therapy strategies in pancreatic cancer.Nature medicine · 2026Trial
- Open-Label, Phase II Trial of Extracellular Regulated Kinase Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer.JCO precision oncology · 2025Trial
- Ligand-activated EGFR/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer.Nature communications · 2025Trial
- Targeting adaptive EGFR feedback enhances the therapeutic efficacy of RMC-6236 in cholangiocarcinoma.Experimental hematology & oncology · 2026Article
- Article
- Review
- Evolving precision: Updates in targeted therapy for cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Review
- Daraxonrasib and the era of pan-RAS inhibition: mechanisms, clinical advances, and resistance landscapes.Experimental hematology & oncology · 2026Review
- Integrated clinicogenomic analysis reveals the evolution and metastatic tropisms of advanced colorectal cancer.Cancer cell · 2026Article
- Engineered subtilisin protease degrades active KRAS in cancer cells leading to differential cell targeting.Research square · 2026Article
- The Landmark Series: Mutation-Based Therapy of Pancreatic Cancer.Annals of surgical oncology · 2026Review
- Thermal Stability, Plasma Pharmacokinetics, and Tumor Response Modeling of a Cell-Penetrating Protein That Cleaves RAS Family GTPases.ACS pharmacology & translational science · 2026Article
- Changes in the transcriptome and synthetic lethal dependencies followingProceedings of the National Academy of Sciences of the United States of America · 2026Article
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- Emerging Therapeutic Strategies for Non-G12C KRAS Mutations in Colorectal Cancer: Focusing on G12D and G12V.Journal of gastrointestinal cancer · 2026Review
- Small-molecule RAS/RAF inhibitors target RAS-driven cancers via allosteric RAF disruption.Nature communications · 2026Article
- Selenium Nanoparticles Selectively Target KRAS G13D to Inhibit Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
153 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
37 authors at 5 institutions in 1 country.
Funding
Abstract
RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models. Translational PK/efficacy and PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, we describe here objective responses in two patients (at 300 mg daily) with advanced KRASG12X lung and pancreatic adenocarcinoma, respectively, demonstrating the initial activity of RMC-6236 in an ongoing phase I/Ib clinical trial (NCT05379985). SIGNIFICANCE: The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors. This article is featured in Selected Articles from This Issue, p. 897.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.