Evidence map›Paper›PMID 38637634›Full record

ReviewNature medicine2024

Targeting KRAS in cancer.

Anupriya Singhal, Bob T Li, Eileen M O'Reilly

Open access · greenAbstract readReview
In one paragraph

Review in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers.

0numbers the graph read from it
0cells of the map it votes in
212citing papers in PubMed
67.0field-weighted citation impact, top 1% of its field
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

212 citing papers in PubMed, 237 citations in OpenAlex.

  1. Trial
  2. A Phase II Trial of an Extended-Release siRNA Implant Targeting KRASG12D/V in Locally Advanced Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Trial
  3. Review
  4. Pancreatic Cancer KRAS Breakthrough: Drug Graveyard No More.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026
    Review
  17. Comparative In Vitro Cytotoxicity ofCurrent issues in molecular biology · 2026
    Article
  18. Review
  19. Article
  20. Targeted therapeutic strategies forTranslational lung cancer research · 2026
    Review

152 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Anupriya SinghalGastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Bob T LiThoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID 0000-0001-6661-8733
Eileen M O'ReillyGastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. oreillye@mskcc.org.ORCID 0000-0002-8076-9199
Memorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Total Neoadjuvant Therapy (TNT) for Borderline Resectable and Locally Advanced Pancreatic AdenocarcinomaP50CA257881 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Christine A Iacobuzio-Donahue · 2022 to 2026
$14.3M
MSK Paul Calabresi Career Development Award for Clinical OncologyK12CA184746 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Omar Abdel-Wahab, Simon N. Powell · 2015 to 2026
$8.3M
NCI NIH HHS K12 CA184746NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA257881
6 · The paper itself

Abstract

RAS family variants-most of which involve KRAS-are the most commonly occurring hotspot mutations in human cancers and are associated with a poor prognosis. For almost four decades, KRAS has been considered undruggable, in part due to its structure, which lacks small-molecule binding sites. But recent developments in bioengineering, organic chemistry and related fields have provided the infrastructure to make direct KRAS targeting possible. The first successes occurred with allele-specific targeting of KRAS p.Gly12Cys (G12C) in non-small cell lung cancer, resulting in regulatory approval of two agents-sotorasib and adagrasib. Inhibitors targeting other variants beyond G12C have shown preliminary antitumor activity in highly refractory malignancies such as pancreatic cancer. Herein, we outline RAS pathobiology with a focus on KRAS, illustrate therapeutic approaches across a variety of malignancies, including emphasis on the 'on' and 'off' switch allele-specific and 'pan' RAS inhibitors, and review immunotherapeutic and other key combination RAS targeting strategies. We summarize mechanistic understanding of de novo and acquired resistance, review combination approaches, emerging technologies and drug development paradigms and outline a blueprint for the future of KRAS therapeutics with anticipated profound clinical impact.

Indexed as

NeoplasmsProto-Oncogene Proteins p21(ras)AllelesAntineoplastic AgentsCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmHumansLung NeoplasmsMutationPancreatic NeoplasmsAntineoplastic AgentsKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID38637634
PMCPMC11845254
OpenAlexW4394931737

What OpenQuestion holds

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Registered trials

None linked

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.