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.

本研究旨在探究雌激素受体阳性（ER+）乳腺癌对CDK4/6抑制剂（CDK4/6i）产生耐药后，基因组不稳定与染色体分离错误的积累情况，并评估有丝分裂激酶抑制剂（mitotic kinase inhibitors）作为CDK4/6抑制剂耐药性乳腺癌患者潜在治疗方案的有效性。本数据集仓库包含腔面型乳腺癌细胞系（T47D、LY2、MDA-MB-361、CAMA1、MCF7、KPL1、ZR751、HCC1428）在未处理的亲本状态以及对帕博西尼（Palbociclib）产生耐药后的全外显子组测序（whole-exome sequencing）与浅层全基因组测序（shallow whole-genome sequencing）数据。帕博西尼耐药模型通过持续逐步递增帕博西尼给药浓度至0.5-1 μM，直至药物存在条件下可观测到细胞增殖（细胞系构建耗时6-8个月）构建而成。在此期间，亲本细胞系在常规培养基中培养，以匹配耐药细胞系的培养时长。耐药性确立后，帕博西尼耐药（Palbo-R）细胞系将在不含帕博西尼的常规生长培养基中培养，并在开展耐药性评估前，至少停用帕博西尼培养两周。