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Article

Synergistic activity and heterogeneous acquired resistance of combined MDM2 and MEK inhibition in KRAS mutant cancers.

Oncogene - 23 Nov 2017

Hata A N, Rowley S, Archibald H L, Gomez-Caraballo M, Siddiqui F M, Ji F, Jung J, Light M, Lee J S, Debussche L, Sidhu S, Sadreyev R I, Watters J, Engelman J A

Abstract excerpt

There are currently no effective targeted therapies for KRAS mutant cancers. Therapeutic strategies that combine MEK inhibitors with agents that target apoptotic pathways may be a promising therapeutic approach. We investigated combining MEK and MDM2 inhibitors as a potential treatment strategy for KRAS mutant non-small cell lung cancers (NSCLC) and colorectal carcinomas that harbor wild-type TP53. The...

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Source

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Identifiers

PMID: 28783173
DOI: 10.1038/onc.2017.258
PMCID: PMC5700857

Genes

MDM2
KRAS

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

Related research

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Synergistic activity and heterogeneous acquired resistance of combined MDM2 and MEK inhibition in KRAS mutant cancers.PMID 28783173Read ↗

Molecular pathways: the basis for rational combination using MEK inhibitors in KRAS-mutant cancers.Semantic proximity Read ↗

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MDM2 antagonists synergize broadly and robustly with compounds targeting fundamental oncogenic signaling pathwaysSemantic proximity Read ↗

RAF suppression synergizes with MEK inhibition in KRAS mutant cancer cells.Semantic proximity Read ↗

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Enhanced apoptosis and tumor growth suppression elicited by combination of MEK (selumetinib) and mTOR kinase inhibitors (AZD8055).Semantic proximity Read ↗

Synergistic two-step inhibition approach using a combination of trametinib and onvansertib in KRAS and TP53-mutated colorectal adenocarcinomaSemantic proximity Read ↗

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Failure to induce apoptosis via BCL-2 family proteins underlies lack of efficacy of combined MEK and PI3K inhibitors for KRAS-mutant lung cancers.Semantic proximity Read ↗

Combined use of PI3K and MEK inhibitors synergistically inhibits lung cancer with EGFR and KRAS mutations.Semantic proximity Read ↗

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PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers.Semantic proximity Read ↗

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