ArticleProceedings of the National Academy of Sciences of the United States of America2020
Tumor regression and resistance mechanisms upon CDK4 and RAF1 inactivation in KRAS/P53 mutant lung adenocarcinomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Stratified and Quantified Score Construction of Low-Grade Glioma Samples Based on TP53 Signaling Pathway.BioMed research international · 2026Article
- RAF1 as a standalone therapeutic target in KRAS-driven lung adenocarcinoma: No added efficacy from co-targeting ARAF, EGFR, or DDR1.PloS one · 2026Article
- Article
- The repressor Capicua is a barrier to lung tumor development driven by Kras/Trp53 mutations.EMBO molecular medicine · 2025Article
- Cryo-shocked tumor cells deliver CRISPR-Cas9 for lung cancer regression by synthetic lethality.Science advances · 2024Article
- The role of CRAF in cancer progression: from molecular mechanisms to precision therapies.Nature reviews. Cancer · 2024Review
- Experimental models for cancer brain metastasis.Cancer pathogenesis and therapy · 2024Review
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Article
- Oncogenic dependency plays a dominant role in the immune response to cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Abemaciclib Is Effective in Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers.Cancer research · 2023Article
- Review
- miR-31/QKI-5 axis facilitates cell cycle progression of non-small-cell lung cancer cells by interacting and regulating p21 and CDK4/6 expressions.Cancer medicine · 2023Article
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
- Targeting KRAS mutant lung cancer: light at the end of the tunnel.Molecular oncology · 2022Review
- Targeting CDK4 overcomes EMT-mediated tumor heterogeneity and therapeutic resistance in KRAS-mutant lung cancer.JCI insight · 2021Article
- Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS mutant lung adenocarcinomas remain intractable for targeted therapies. Genetic interrogation of KRAS downstream effectors, including the MAPK pathway and the interphase CDKs, identified CDK4 and RAF1 as the only targets whose genetic inactivation induces therapeutic responses without causing unacceptable toxicities. Concomitant CDK4 inactivation and RAF1 ablation prevented tumor progression and induced complete regression in 25% of KRAS/p53-driven advanced lung tumors, yet a significant percentage of those tumors that underwent partial regression retained a population of CDK4/RAF1-resistant cells. Characterization of these cells revealed two independent resistance mechanisms implicating hypermethylation of several tumor suppressors and increased PI3K activity. Importantly, these CDK4/RAF1-resistant cells can be pharmacologically controlled. These studies open the door to new therapeutic strategies to treat KRAS mutant lung cancer, including resistant tumors.
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