The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER+ breast cancer with mitotic aberrations

This study aims to investigate the accumulation of genomic instability and chromosome segregation errors after the acquisition of resistance to CDK4/6i in ER+ breast cancer and to test the efficacy of mitotic kinase inhibitors as a potential treatment for CDK4/6i-resistant breast cancer patients. This repository contains whole-exome and shallow whole-genome sequencing from luminal breast cancer cell lines (T47D, LY2, MDA-MB-361, CAMA1, MCF7, KPL1, ZR751, HCC1428) both at the untreated or Parental state and post resistance to Palbociclib. Palbociclib resistance was developed by continuous dose-escalation of palbociclib up to 0.5-1 uM until cell growth was observed in the presence of the drug (6-8 months for cell lines). During this time, parental cell lines were cultured in regular media to match the time spent in culture. Once resistance was established, Palbo-R cell lines were cultured in a regular growth medium without palbociclib. Cells were cultured without palbociclib for at least two weeks before evaluating resistance.