What does this research mean for the field?

Autophagy activation serves as a key adaptive mechanism driving acquired resistance to PI3K inhibitors such as taselisib in breast cancer. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

The aim is to understand the mechanisms of resistance to PI3K inhibitors in breast cancer, focusing on autophagy.

February 19, 2026Clinical Cancer Research

Abstract PS2-11-11: Mechanisms of Acquired Resistance to PI3K Inhibitors in Breast Cancer: The Central Role of Autophagy

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Authors

BPBiagio PucciIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale"RLR. LombardiIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale"TMTania MocciaIstituto Nazionale Tumori IRCCS "Fondazione G. Pascale"

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Implication

Demonstrates how autophagy contributes to resistance against PI3K inhibitors in breast cancer, suggesting new treatment strategies.

Key Points

The aim is to understand the mechanisms of resistance to PI3K inhibitors in breast cancer, focusing on autophagy.
Developed a resistant cell line (MCF7 Tas-r) using stepwise taselisib exposure.
Conducted phosphoproteomic profiling to identify differentially phosphorylated proteins.
Performed functional enrichment analysis to determine pathways affected by resistance.
Validated findings with Western blot analysis of key proteins involved in PI3K and autophagy signaling.
Identified 253 differentially phosphorylated proteins in resistant cells compared to parental cells.
Functional analysis revealed significant enrichment in autophagy pathways, particularly mTOR and AMPK signaling.
Increased levels of phosphorylated AMPK and decreased phosphorylated mTOR were observed in resistant cells.
Chloroquine treatment enhanced the effectiveness of taselisib in vitro.

Cite This Study

Pucci et al. (2026) studied this question.

synapsesocial.com/papers/6996a8efecb39a600b3f02c5 https://doi.org/10.1158/1557-3265.sabcs25-ps2-11-11

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Abstract PS2-11-11: Mechanisms of Acquired Resistance to PI3K Inhibitors in Breast Cancer: The Central Role of Autophagy

Discussion

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Implication

Key Points

Cite This Study

Abstract PS2-11-11: Mechanisms of Acquired Resistance to PI3K Inhibitors in Breast Cancer: The Central Role of Autophagy

Discussion

Member takes

Implication

Key Points

Cite This Study

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