Brewer Gabrielle, Fortier Anne-Marie, Park Morag, Moraes Christopher
Rosalind & Morris Goodman Cancer Research Centre, McGill University, 1160 Avenues des Pins, Montréal, QC, H3A 0G4, Canada.
Department of Biochemistry, McGill University, 3649 Promenade Sir-William-Osler, Montréal, QC, H3A 0G4, Canada.
Future Drug Discov. 2022 Jan;4(1):FDD71. doi: 10.4155/fdd-2021-0004. Epub 2021 Mar 30.
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.
尽管癌症相关成纤维细胞（CAFs）因支持癌症进展而受到越来越多的关注，但目前针对CAFs的治疗选择有限，且在临床试验中失败。作为肿瘤微环境（TME）的最大组成部分，CAFs改变了TME的生化和物理结构，调节癌症进展。在这里，我们综述了CAFs在改变药物反应、改变TME力学方面的作用以及目前研究CAFs的模型。为了提供新的视角，我们强调了CAF活性的关键考虑因素，并讨论了能够更好地应对CAFs的新兴技术；因此，提高治疗效果的可能性。我们认为，CAFs是癌症药物研发流程的关键组成部分，纳入这些细胞将提高药物研发成功率。
