Chapter 7 - Autophagy in cancer-associated fibroblasts: biology and targeting

Abstract

The tumor microenvironment (TME) plays a key role in cancer progression and cancer treatment. Cancer-associated fibroblast (CAF), a major component in TME, is essential in cancer initiation and progression. In most cases, CAFs promote cancer progression, although there have been conflicting reports where depleting CAFs accelerated cancer aggressiveness, necessitating a deeper understanding of CAFs. CAFs are not uniform cell populations but rather reflect the epigenetic state of cells derived from diverse sources, hence, diverse in their markers, phenotype, and function in cancer progression. This could be a possible source of heterogeneity in CAF responses to targeting. Autophagy, a unique catabolic cellular process, is significantly higher in CAFs than in normal fibroblasts and is an important mechanism by which CAFs maintain their phenotype. Furthermore, autophagy in CAFs generates amino acids, growth factors, and cytokines that promote cancer progression through intricate crosstalk between CAFs and the microenvironment. Given the essential role of CAF autophagy in cancer progression, targeting CAF autophagy opens an exciting avenue in developing oncologic treatment.