Bridging the divide: preclinical research discrepancies between triple-negative breast cancer cell lines and patient tumors

Abstract

Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer and disproportionately accounts for the majority of breast cancer related deaths. Effective treatment of this disease remains an unmet medical need. Over the past several decades, TNBC cell lines have been used as the foundation for drug development and disease modeling. However, ever-mounting research demonstrates striking differences between cell lines and clinical TNBC tumors, disconnecting bench research and actual clinical responses. In this review, we discuss the limitations of cell lines and the importance of using patients’ tumors for translational research, and highlight the usage of patient-derived xenograft (PDXs) models that have emerged as a clinically relevant platform for preclinical studies. PDX tumors possess tumor heterogeneity with similar cellular, molecular, genetic and epigenetic properties akin to those found within patients’ tumors. Moreover, PDX and clinical tumors possess abnormal vasculature with higher blood vessel permeability, a feature that is not always demonstrated in in vivo cell line xenografts. Development of clinically relevant, novel drug-nanoparticles capable of accumulating in PDX tumors through the enhanced permeability and retention effect in tumor vasculature may lead to new and effective TNBC treatments.