Abstract
Various new drugs have been developed for treating recurrent hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2−) breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent HR+/HER2− metastatic breast cancer. The recently established conditionally reprogrammed (CR) cell system enables us to examine heterogeneity, drug sensitivity and cell function using patient-derived tumour samples. The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumour cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with gene expression profiling test data. We performed drug-screening assays using liver metastases, which were sensitive to 66 drugs. Importantly, the result reflected the actual clinical course of this patient. These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2− breast cancer for predicting the clinical drug efficacy.
Highlights
Various new drugs, including a selective oestrogen receptor degrader (SERD), the mammalian target of rapamycin inhibitor, PI3K inhibitor and cyclin-dependent kinase (CDK)4/6 inhibitor, have been developed for recurrent hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2−) breast cancer[1,2,3,4,5]
In this study, we aimed to reveal the characteristics of breast cancer Conditionally reprogrammed (CR) cells and clarify whether drug sensitivity assays using CR cells taken from patients with HR+/HER2− metastatic breast cancer are useful for assessing drug efficacy in consideration of their potential clinical application
In four of five patients with HR+/HER2− tumours, CR cells could be produced within 2 weeks (Fig. 1B,C)
Summary
Various new drugs, including a selective oestrogen receptor degrader (SERD), the mammalian target of rapamycin (mTOR) inhibitor, PI3K inhibitor and cyclin-dependent kinase (CDK)4/6 inhibitor, have been developed for recurrent hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2−) breast cancer[1,2,3,4,5]. The genomic and histological features of the original tumour are maintained in CR cells[17,18,19] This method makes it possible to directly assess drug sensitivity and conduct molecular analysis in individual cancer patients. It has been reported that CR cells were useful for identifying effective treatments for respiratory papillomatosis[20], adenoid cystic carcinoma[21], pancreatic cancer[22] and prostate cancer[23,24] Inspired by these results, in this study, we aimed to reveal the characteristics of breast cancer CR cells and clarify whether drug sensitivity assays using CR cells taken from patients with HR+/HER2− metastatic breast cancer are useful for assessing drug efficacy in consideration of their potential clinical application
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