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. <strong>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</strong>. 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.本研究旨在探究雌激素受体阳性（ER+）乳腺癌患者对CDK4/6抑制剂（CDK4/6i）产生耐药性后，基因组不稳定性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。**本数据集库包含来自管腔型乳腺癌患者来源类器官（BPTO.95 #1与#2）的全外显子组测序及浅层全基因组测序数据，样本分别取自未处理的亲本状态以及对帕博西尼（Palbociclib）产生耐药性后的状态。**帕博西尼耐药模型的构建方式为：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（患者来源类器官的构建周期为10-12个月）。在此期间，亲本细胞系与类器官均培养于常规培养基中，以匹配耐药构建过程中的培养时长。耐药性确立后，帕博西尼耐药类器官（Palbo-R PDOs）将被转移至不含帕博西尼的常规生长培养基中培养，并在停用帕博西尼至少两周后开展耐药性评估。