Tumour kinome re-wiring governs resistance to palbociclib in estrogen receptor positive breast cancers

Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcomein advanced estrogen receptor (ER)-positive breast cancer, however relapse isinevitable. Human breast cancer cell lines that have undergone long term estrogen deprivation were cultured in 1uM palbociclib until resistance developed. Exome sequencing was undertaken to identify mutations and copy number alterations associated with resistance.

CDK4/6抑制剂联合内分泌治疗可改善晚期雌激素受体（ER）阳性乳腺癌的临床结局，但肿瘤复发仍不可避免。本研究将经长期雌激素剥夺培养的人乳腺癌细胞系置于1μM帕博西尼（palbociclib）中持续培养直至其产生耐药性，随后通过外显子测序（exome sequencing）鉴定与耐药相关的基因突变及拷贝数变异。