Evidence map›Paper›PMID 42685085›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Changes in the transcriptome and synthetic lethal dependencies following

Timothy D Martin, Mei Yuk Choi, Julia C McBride, Stephen J Elledge

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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. Changes in the transcriptome and synthetic lethal dependencies followingProceedings of the National Academy of Sciences of the United States of America · 2026
    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

4 authors.

Timothy D MartinHHMI, Department of Genetics, Harvard University Medical School, Boston, MA 02115.ORCID 0000-0002-4870-3624
Mei Yuk ChoiHHMI, Department of Genetics, Harvard University Medical School, Boston, MA 02115.
Julia C McBrideHHMI, Department of Genetics, Harvard University Medical School, Boston, MA 02115.ORCID 0009-0002-7651-7957
Stephen J ElledgeHHMI, Department of Genetics, Harvard University Medical School, Boston, MA 02115.ORCID 0000-0001-7923-6283

Funding

Cancer Research UK (CRUK) noneHHMI (HHMI) NoneLudwig Family Foundation (The Ludwig Family Foundation) NoneMark Foundation For Cancer Research (MFCR) none
6 · The paper itself

Abstract

Oncogenic KRAS mutations exhibit a striking tissue-restricted tropism, occurring with high frequency in pancreatic, colorectal, and lung adenocarcinomas while remaining rare in other lineages. The molecular basis for why these specific tissues are uniquely permissive to KRAS transformation, and how this context shapes therapeutic vulnerabilities, remains poorly defined. Here, we utilized CRISPR-mediated genome engineering to generate endogenous, conditional KRAS-mutant isogenic cell line models across three primary permissive lineages (lung, colon, and pancreas) and the nonpermissive breast lineage. Integrated genome-wide CRISPR fitness screens and comparative transcriptome analyses revealed that KRAS-driven synthetic lethal (SL) dependencies are profoundly shaped by their tissue of origin. Strikingly, we observed minimal overlap in SL hits across lineages, with only three genes shared among the permissive lines, suggesting that the

Indexed as

MutationProto-Oncogene Proteins p21(ras)Synthetic Lethal MutationsTranscriptomeAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansOrgan SpecificityKRAS protein, humanProto-Oncogene Proteins p21(ras)cancerKRASsynthetic lethalitytissue specificity

Identifiers

PMID42685085
PMCPMC13552922

What Socratic holds

Textmetadata
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 Socratic graph.