Fig. 3

Roles of circRNAs in mechanisms mediating radioresistance and chemoresistance of cancers. In tumor microenvironment (TME), microorganisms modulate the critical chemical structures or local concentrations of drugs. In addition to regulating the distribution of drugs, noncancerous cells, such as CAFs and CAMs, can secrete soluble factors to promote therapy resistance. Remodeling of transporters or channels responsible for drug flux could result in decreased intracellular drug concentration. Amplification of targets or activation of aberrant downstream signals also impedes therapeutic efficacy by inducing ER stress, autophagy, mitophagy, stemness and DNA repair