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Article

Dual PI3K/mTOR inhibition is required to combat resistance to CDK4/6 inhibitor and endocrine therapy in PIK3CA-mutant breast cancer.

Science translational medicine - 17 Dec 2025

Alves Carla L, Karimi Leena, Terp Mikkel G, Jakobsen Mie K, Zhou Fiona H, Policastro Benedetta, Nissen Nikoline, Johansen Lene E, Ravnsborg Tina, Eshraghi Leila, Tamboowala Sana, Jensen Ole N, Lim Elgene, Ditzel Henrik J

Abstract excerpt

Combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy (ET) improves outcomes in advanced estrogen receptor-positive (ER+) breast cancer, but emergence of resistance to this combination underscores the pressing need for alternative therapeutic strategies. A promising approach involves adding an inhibitor of the PI3K/AKT/mTOR pathway to the standard combined CDK4/6i and ET, but selecting the most effective...

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Identifiers

PMID: 41406241
DOI: 10.1126/scitranslmed.adp5088

Genes

CDK4
PIK3CA
PTEN
AKT1

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 3 Sept 2026.

Related research

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Dual PI3K/mTOR inhibition is required to combat resistance to CDK4/6 inhibitor and endocrine therapy in PIK3CA-mutant breast cancer.PMID 41406241Read ↗

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Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancerSemantic proximity Read ↗

CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors.Semantic proximity Read ↗

Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models.Semantic proximity Read ↗

PI3K inhibition in breast cancer: Identifying and overcoming different flavors of resistance.Semantic proximity Read ↗

Beyond CDK4/6 Inhibition: Current Strategies in Hormone Receptor-Positive Metastatic Breast Cancer.Semantic proximity Read ↗

PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trialsSemantic proximity Read ↗

Promising rationally derived combination therapy with PI3K and CDK4/6 inhibitors.Semantic proximity Read ↗

Inavolisib-based Combination Therapy for the Treatment of PIK3CAMutated HR+/HER2- Breast Cancer: An Overview.Semantic proximity Read ↗

A Phase Ib Study of Alpelisib (BYL719), a PI3Kα-Specific Inhibitor, with Letrozole in ER+/HER2- Metastatic Breast Cancer.Semantic proximity Read ↗

Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer.Semantic proximity Read ↗

Targeting the PI3K/Akt/mTOR pathway: Effective combinations and clinical considerationsSemantic proximity Read ↗

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