The case for cancer-associated fibroblasts: essential elements in cancer drug discovery?

ABSTRACT

Although cancer-associated fibroblasts (CAFs) have gained increased attention for supporting cancer progression, current CAF-targeted therapeutic options are limited and failing in clinical trials. As the largest component of the tumor microenvironment (TME), CAFs alter the biochemical and physical structure of the TME, modulating cancer progression. Here, we review the role of CAFs in altering drug response, modifying the TME mechanics and the current models for studying CAFs. To provide new perspectives, we highlight key considerations of CAF activity and discuss emerging technologies that can better address CAFs; and therefore, increase the likelihood of therapeutic efficacy. We argue that CAFs are crucial components of the cancer drug discovery pipeline and incorporating these cells will improve drug discovery success rates.

Recent advances in cancer research have improved our understanding of disease progression; however, the number of drugs failing in clinical trials remains high and therefore, present a critical challenge for cancer drug discovery. Although the interactions of the tissue surrounding the tumor, the tumor microenvironment, are now considered key targets for new interventions in cancer, the role of microenvironment is largely absent in drug discovery pipelines. Here we explore the role of the most prominent cell type in the tumor microenvironment, cancer-associated fibroblasts (CAFs), in altering cancer therapy response and ultimately patient outcome. To provide new perspectives for future studies, we draw attention to key complications of CAF biology and highlight emerging technologies that could be used to address this. We believe including CAFs in drug discovery, whether for targeting cancer cells or the microenvironment, will allow for a better understanding of therapeutic efficacy and ultimately improve clinical outcome.