Evidence map›Paper›PMID 36065754›Full record

ArticleThe Biochemical journal2022

Combinatorial approaches for mitigating resistance to KRAS-targeted therapies.

Hannah R Warren, Sarah J Ross, Paul D Smith, Judy M Coulson, Ian A Prior

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 38% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
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

5 authors at 2 institutions in 1 country.

Hannah R WarrenDepartment of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, U.K.
Sarah J RossOncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K.
Paul D SmithOncology R&D, AstraZeneca, Cambridge CB2 0AA, U.K.
Judy M CoulsonDepartment of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, U.K.
Ian A PriorDepartment of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, U.K.ORCID 0000-0002-4055-5161
University of Liverpool · GBAstraZeneca (United Kingdom) · GB

Funding

Wellcome Trust WT204002
6 · The paper itself

Abstract

Approximately 15% of all cancer patients harbor mutated KRAS. Direct inhibitors of KRAS have now been generated and are beginning to make progress through clinical trials. These include a suite of inhibitors targeting the KRASG12C mutation commonly found in lung cancer. We investigated emergent resistance to representative examples of different classes of Ras targeted therapies. They all exhibited rapid reactivation of Ras signaling within days of exposure and adaptive responses continued to change over long-term treatment schedules. Whilst the gene signatures were distinct for each inhibitor, they commonly involved up-regulation of upstream nodes promoting mutant and wild-type Ras activation. Experiments to reverse resistance unfortunately revealed frequent desensitization to members of a panel of anti-cancer therapeutics, suggesting that salvage approaches are unlikely to be feasible. Instead, we identified triple inhibitor combinations that resulted in more durable responses to KRAS inhibitors and that may benefit from further pre-clinical evaluation.

Indexed as

Lung NeoplasmsProto-Oncogene Proteins p21(ras)HumansMutationSignal TransductionKRAS protein, humanProto-Oncogene Proteins p21(ras)drug resistanceG-proteinssignaling

Identifiers

PMID36065754
PMCPMC9555794
OpenAlexW4294723822

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.