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 patient-derived organoid (BPTO.95 #1 and #2) 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 μM until cell growth was observed in the presence of the drug (10-12 months for PDO). During this time, parental cell lines and organoids were cultured in regular media to match the time spent in culture. Once resistance was established, Palbo-R PDOs were cultured in a regular growth medium without palbociclib. Cells were cultured without palbociclib for at least two weeks before evaluating resistance.