Current perspectives on the crosstalk between lung cancer stem cells and cancer-associated fibroblasts

Lung cancer, in particular non-small cell lung carcinoma (NSCLC), is the second most common cancer in both men and women and the leading cause of cancer-related deaths worldwide. Its prognosis and diagnosis are determined by several driver mutations and diverse risk factors (e.g. smoking). While immunotherapy has proven effective in some patients, treatment of NSCLC using conventional chemotherapy is largely ineffective. The latter is believed to be due to the existence of a subpopulation of stem-like, highly tumorigenic and chemoresistant cells within the tumor population known as cancer stem cells (CSC). To complicate the situation, CSCs interact with the tumor microenvironment, which include cancer-associated fibroblasts (CAFs), immune cells, endothelial cells, growth factors, cytokines and connective tissue components, which via a dynamic crosstalk, composed of proteins and exosomes, activates the CSC compartment. In this review, we analyze the crosstalk between CSCs and CAFs, the primary component of the NSCLC microenvironment, at the molecular and extracellular level and contemplate therapies to disrupt this communication.