Proteomics

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Phosphoproteomics of BYL719 (alpelisib)-Resistant T47D Human Breast Cancer Cell Line


ABSTRACT: The PI3Kalpha-specific inhibitor Alpelisib (BYL719) has been approved for the treatment of metastatic ER+/HER2- breast cancer patients in combination with Fulvestrant. After initial response, patients develop drug resistance and disease relapses. In order to identify signalling pathways contributing to the acquired resistance to BYL719 in breast cancer, we generated BYL719-resistant T47D cells and used them together with the parental cells to perform label-free quantitative phosphoproteomics.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Kelvin Yip  

LAB HEAD: Antonella Papa

PROVIDER: PXD033956 | Pride | 2023-12-05

REPOSITORIES: Pride

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Publications

Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.

Yip Hon Yan Kelvin HYK   Shin Sung-Young SY   Chee Annabel A   Ang Ching-Seng CS   Rossello Fernando J FJ   Wong Lee Hwa LH   Nguyen Lan K LK   Papa Antonella A  

NPJ precision oncology 20240126 1


Utility of PI3Kα inhibitors like BYL719 is limited by the acquisition of genetic and non-genetic mechanisms of resistance which cause disease recurrence. Several combination therapies based on PI3K inhibition have been proposed, but a way to systematically prioritize them for breast cancer treatment is still missing. By integrating published and in-house studies, we have developed in silico models that quantitatively capture dynamics of PI3K signaling at the network-level under a BYL719-sensitiv  ...[more]

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