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Updated: Sep 5, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Proteomic characterisation of triple negative breast cancer cells following CDK4/6 inhibition
Melina Beykou1,2,3, Mar Arias-Garcia4, Theodoros I Roumeliotis5
1Imperial College London, Department of Electrical and Electronic Engineering, Circuits and Systems Group, South Kensington Campus, London, SW7 2AZ, UK. melina.beykou19@imperial.ac.uk.
Abstract:
When used in combination with hormone treatment, Palbociclib prolongs progression-free survival of patients with hormone receptor positive breast cancer. Mechanistically, Palbociclib inhibits CDK4/6 activity but the basis for differing sensitivity of cancer to Palbociclib is poorly understood. A common observation in a subset of Triple Negative Breast Cancers (TNBCs) is that prolonged CDK4/6 inhibition can engage a senescence-like state where cells exit the cell cycle, whilst, remaining metabolically active. To better understand the senescence-like cell state which arises after Palbociclib treatment we used mass spectrometry to quantify the proteome, phosphoproteome, and secretome of Palbociclib-treated MDA-MB-231 TNBC cells. We observed altered levels of cell cycle regulators, immune response, and key senescence markers upon Palbociclib treatment. These datasets provide a starting point for the derivation of biomarkers which could inform the future use CDK4/6 inhibitors in TNBC subtypes and guide the development of potential combination therapies.
Insights
Palbociclib, a CDK4/6 inhibitor, can induce a senescence-like state in Triple Negative Breast Cancer (TNBC) cells. This study quantifies proteomic changes to identify biomarkers for TNBC treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Palbociclib is a CDK4/6 inhibitor that improves progression-free survival in hormone receptor-positive breast cancer.
- The mechanism of differential cancer sensitivity to Palbociclib is not fully understood.
- Prolonged CDK4/6 inhibition in some Triple Negative Breast Cancers (TNBCs) induces a senescence-like state.
Purpose of the Study:
- To investigate the molecular changes associated with the senescence-like state induced by Palbociclib in TNBC cells.
- To identify potential biomarkers for predicting response to CDK4/6 inhibitors in TNBC subtypes.
- To explore novel combination therapies for TNBC.
Main Methods:
- Quantitative proteomic, phosphoproteomic, and secretomic analysis using mass spectrometry.
- Treatment of MDA-MB-231 TNBC cells with Palbociclib.
- Analysis of cell cycle regulators, immune response markers, and senescence markers.
Main Results:
- Palbociclib treatment altered the levels of cell cycle regulators.
- Key senescence markers were found to be differentially expressed.
- Changes in immune response pathways were observed in treated cells.
Conclusions:
- The study provides comprehensive proteomic datasets of Palbociclib-induced senescence in TNBC.
- These findings can aid in developing biomarkers for CDK4/6 inhibitor therapy in TNBC.
- The results may guide the development of combination therapies targeting TNBC subtypes.
