Evidence map›Paper›PMID 42557306›Full record

ArticleOncogene2026

M1C is a druggable target for NSCLC KRAS G12C mutant tumors resistant to KRAS inhibitors.

Shinkichi Takamori, Naoki Haratake, Atrayee Bhattacharya, Hiroki Ozawa, Keisuke Shigeta, Mai Onishi, Kentaro Nonaka, Takefumi Komiya, Hiroki Komatsuda, Tomoyoshi Takenaka and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 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. 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

17 authors.

Shinkichi TakamoriDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Naoki HaratakeDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Atrayee BhattacharyaDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Hiroki OzawaDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3771-7940
Keisuke ShigetaDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Mai OnishiDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Kentaro NonakaDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Takefumi KomiyaDivision of Hematology and Oncology Penn State College of Medicine, Hershey, PA, USA.
Hiroki KomatsudaDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA.
Tomoyoshi TakenakaDepartment of Surgery and Science Graduate School of Medical Sciences Kyushu University, Fukuoka, Japan.
Tomoharu YoshizumiDepartment of Surgery and Science Graduate School of Medical Sciences Kyushu University, Fukuoka, Japan.ORCID http://orcid.org/0000-0002-4497-1816
Chendi LiDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jiehui DengLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
Aaron N HataDepartment of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6127-318X
Kwok K WongLaura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-6323-235X
Mark D LongDepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.ORCID http://orcid.org/0000-0003-1120-8176
Donald KufeDepartment of Medical Oncology Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA. Donald_Kufe@dfci.harvard.edu.ORCID http://orcid.org/0000-0001-5743-8888

Funding

Targeting the MUC1-C Oncoprotein in Triple-Negative Breast CancerR01CA097098 · NCI · DANA-FARBER CANCER INSTITUTE · PI DONALD W. KUFE · 2002 to 2026
$8.8M
Combining CDK7 and MUC1-C inhibition to target different subtypes of small cell lung cancerR01CA282437 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DONALD W. KUFE, Kwok Kin Wong · 2024 to 2026
$2.1M
MUC1-C is a target for advancing immunotherapy of non-small cell lung cancerR21CA289134 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W. · 2024 to 2024
$450k
NCI NIH HHS R01 CA097098NCI NIH HHS R01 CA282437NCI NIH HHS R21 CA289134U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA282437U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA289134U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA97098
6 · The paper itself

Abstract

Treatment of NSCLC KRAS G12C mutant tumors with the allele-selective sotorasib and adagrasib inhibitors is invariably associated with acquired resistance. The MUC1-encoded oncogenic M1C protein is necessary for self-renewal of NSCLC KRAS mutant cells. We report that treatment of NSCLC KRAS G12C cells with sotorasib induces M1C expression by a STAT1-dependent pathway. In turn, M1C drives the sotorasib resistant phenotype by NF-κB-mediated induction of the epithelial-mesenchymal transition (EMT) and a mucinous gene program. Targeting M1C→NF-κB signaling (i) suppresses EMT and mucin genes, and (ii) reverses sotorasib resistance. Of translational relevance, treatment with a M1C antibody-drug conjugate (ADC) is effective against two sotorasib-resistant NSCLC KRAS G12C cell lines and two patient-derived tumor xenograft models. Analysis of patients with NSCLC KRAS G12C tumors treated with sotorasib/adagrasib and overexpressing MUC1 associates with decreases in overall survival. These findings identify M1C as a key effector of sotorasib resistance and as a target for treatment of patients with refractory NSCLC KRAS G12C mutant tumors.

Indexed as

Carcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmLung NeoplasmsMucin-1Proto-Oncogene Proteins p21(ras)AnimalsCell Line, TumorEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMiceMutationNF-kappa BPiperazinesPyridinesKRAS protein, humanMUC1 protein, humanMucin-1NF-kappa BPiperazinesProto-Oncogene Proteins p21(ras)PyridinesPyrimidinessotorasibSTAT1 protein, humanSTAT1 Transcription Factor

Identifiers

PMID42557306
PMCPMC13577901

What OpenQuestion holds

Textmetadata
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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.