Publication:
Novel combination treatment of CDK 4/6 inhibitors with PARP inhibitors in triple negative breast cancer cells.

No Thumbnail Available
Date
2023-04-30T21:00:00Z
Authors
Authors
Guney Eskiler, Gamze
Ozman, Zeynep
Haciefendi, Ayten
Cansaran-Duman, Demet
Journal Title
Journal ISSN
Volume Title
Publisher
Research Projects
Organizational Units
Journal Issue

Metrics

Search on Google Scholar

Abstract
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors provide promising results for treating hormone receptor-positive breast cancer. However, the efficacy of CDK4/6 inhibitors remains uncertain in triple negative breast cancer (TNBC) patients with particularly carrying RB-deficient tumors. Poly-(ADP-ribose) polymerase (PARP) inhibitors offer a therapeutic strategy for the treatment of BRCA-mutated TNBC patients. However, the acquired drug resistance, changes in the cell cycle regulation, and DNA damage repair have demonstrated the necessity for developing new combination strategies. This preclinical study assessed a combinatory treatment of the CDK4/6 inhibitor abemaciclib with PARP inhibitors talazoparib (TAL) in HCC1937 BRCA-mutated RB-deficient TNBC cells and TAL-resistant HCC1937-R cells through WST-1 analysis, annexin V, cell cycle, acridine orange/propidium iodide staining, RT-PCR, and apoptosis array. Our findings revealed that abemaciclib and TAL combination synergistically suppressed the growth of TNBC cells and overcame TAL resistance through G0/G1 arrest and the activity of both intrinsic and extrinsic apoptotic pathways. These preliminary results suggest that the combination of abemaciclib and TAL could expand the use of these inhibitors in BRCA mutated and RB deficient TNBC patients and potentially overcomes PARP inhibitors resistance.
Description
Keywords
Abemaciclib, Apoptosis, Resistance, Talazoparib, Triple-negative breast cancer
Citation
Page Views

1

File Downloads

0

Sustainable Development Goals