The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ER+ breast cancer with mitotic aberrations
Authors/Creators
- 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 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 μM until cell growth was observed in the presence of the drug (6-8 months for cell lines). 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 cell lines were cultured in a regular growth medium without palbociclib. Cells were cultured without palbociclib for at least two weeks before evaluating resistance.
Notes
Files
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