Evidence map›Paper›PMID 42678463›Full record

ReviewJournal of gastrointestinal cancer2026

Emerging Therapeutic Strategies for Non-G12C KRAS Mutations in Colorectal Cancer: Focusing on G12D and G12V.

Tamotsu Sagawa, Masahiro Hirakawa, Hiroyuki Nagashima, Koshi Fujikawa

Abstract readReview
PubMed Publisher
In one paragraph

Review in Journal of gastrointestinal cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Tamotsu SagawaDepartment of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, 3-54 Kikusui 4-jo 2-chome, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan. sagawa.tamotsu.dy@mail.hosp.go.jp.ORCID http://orcid.org/0000-0002-1994-4795
Masahiro HirakawaDivision of Medical Oncology, Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hiroyuki NagashimaDepartment of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, 3-54 Kikusui 4-jo 2-chome, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan.
Koshi FujikawaDepartment of Gastroenterology, National Hospital Organization Hokkaido Cancer Center, 3-54 Kikusui 4-jo 2-chome, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeKRAS mutations are present in approximately 40-45% of colorectal cancers (CRC), but currently approved KRAS-directed therapies address only the small G12C subset. G12D and G12V account for a much larger proportion of KRAS-mutant CRC and remain major unmet therapeutic targets. This review summarizes emerging strategies for non-G12C KRAS-mutant CRC.

methodsCurrent preclinical, translational, and early clinical evidence was narratively synthesized, focusing on allele-specific G12D and G12V inhibitors, pan-RAS approaches, upstream SOS1/SHP2 co-targeting, anti-EGFR combinations, immune-based strategies, and tissue and circulating tumor DNA profiling.

resultsThe development of MRTX1133, zoldonrasib (RMC-9805), VS-7375, RMC-5127, and daraxonrasib (RMC-6236) demonstrates that direct targeting of previously undruggable KRAS alleles is becoming clinically feasible. In CRC, however, EGFR-mediated feedback reactivation of wild-type RAS remains a central resistance mechanism, making anti-EGFR combination strategies particularly important.Tissue and circulating tumor DNA profiling may support patient selection, monitoring of clonal evolution, and characterization of acquired resistance.

conclusionThe non-G12C KRAS era is beginning, but durable benefit in CRC will likely require rational combinations tailored to allele, lineage, and resistance biology.

Indexed as

Antineoplastic AgentsColorectal NeoplasmsProto-Oncogene Proteins p21(ras)AnimalsHumansMolecular Targeted TherapyMutationAntineoplastic AgentsKRAS protein, humanProto-Oncogene Proteins p21(ras)Colorectal cancerKRAS G12DKRAS G12VKRAS inhibitorMolecular glueTargeted therapy

Identifiers

PMID42678463

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.