Metastasis is the most common cause of cancer-related death and, as such, there is an urgent need to discover new therapies to treat metastasized cancers. Cancer cell lines are widely-used models to study cancer biology and evaluate drug candidates. However, it is still unknown whether they adequately recapitulate the disease in patients. The recent accumulation of large-scale genomic data in cell lines, mouse models, and patient tissue samples provides an unprecedented opportunity to evaluate the suitability of cancer cell lines as models for metastatic cancer research. Through comprehensively comparing the genomic profiles of 57 breast cancer cell lines with those of metastatic breast cancer samples, we found their substantial genomic differences. We also identified cell lines that more closely resemble different subtypes of metastatic breast cancer. However, we found none of the currently established Basal-like cell lines sufficiently resemble the samples of Basal-like metastatic breast cancer, a subtype of high interest in therapeutic discovery. Further analysis of mutation, copy number variation and gene expression data suggested that MDAMB231, the most commonly used triple negative cell line, had little genomic similarity with Basal-like metastatic breast cancer samples. Our work demonstrates an urgent need of cell lines that more closely resemble Basal-like metastatic breast cancer samples, and could guide cell line selection in other metastasis-related translational research.

Evaluating cell lines as models for metastatic cancer through integrative analysis of open genomic data