The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER+ breast cancer with mitotic aberrations
- Soria-Bretones, Isabel1
- Thu, Kelsie2
- Silvester, Jennifer3
- Cruickshank, Jennifer3
- El Ghamrasni, Samah3
- Ba-alawi, Wail3
- Fletcher, Graham C4
- Kiarash, Reza3
- Elliott, Mitchell J.5
- Chalmers, Jordan J.3
- Elia, Andrea C.3
- Cheng, Albert3
- Rose, April A. N.6
- Bray, Mark R.7
- Haibe-Kains, Benjamin3
- Mak, Tak W.3
- Cescon, David W.5
- 1. Princess Margaret Cancer Centre, University Health Network; Toronto (ON), Canada; Segal Cancer Centre & Lady Davis Institute for Medical Research, Jewish General Hospital; Montreal (QC), Canada; Gerald Bronfman Department of Oncology, McGill University; Montreal (QC), Canada; Current affiliation: Repare Therapeutics; Montreal (QC), Canada
- 2. Princess Margaret Cancer Centre, University Health Network; Toronto (ON), Canada; Keenan Research Centre for Biomedical Sciences, St. Michael's Hospital; Toronto (ON), Canada; Laboratory Medicine and Pathobiology, University of Toronto; Toronto (ON), Canada
- 3. Princess Margaret Cancer Centre, University Health Network; Toronto (ON), Canada
- 4. Princess Margaret Cancer Centre, University Health Network; Toronto (ON), Canada; urrent affiliation: Treadwell Therapeutics; Toronto (ON), Canada
- 5. Princess Margaret Cancer Centre, University Health Network; Toronto (ON), Canada; Department of Medicine, University of Toronto; Toronto (ON), Canada
- 6. Segal Cancer Centre & Lady Davis Institute for Medical Research, Jewish General Hospital; Montreal (QC), Canada; Gerald Bronfman Department of Oncology, McGill University; Montreal (QC), Canada
- 7. Princess Margaret Cancer Centre, University Health Network; Toronto (ON), Canada; Current affiliation: Treadwell Therapeutics; Toronto (ON), Canada
Description
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.
Files
Restricted
The record is publicly accessible, but files are restricted. Log in to check if you have access.