Cell-intrinsic survival signals. The role of autophagy in metastatic dissemination and tumor cell dormancy.

ABSTRACT

Metastasis is the main cause of cancer-related deaths. Disseminated tumor cells (DTCs), which seed metastasis, can remain undetected in a dormant state for decades after treatment of the primary tumor and their persistence is the main cause of late relapse and death in a substantial proportion of cancer patients. Understanding the mechanisms underlying the survival of dormant DTCs is of utmost importance to develop new therapies that effectively kill DTCs while in a quiescent state, therefore preventing metastatic disease and minimizing the chance of future relapses. Besides key interactions with the local microenvironment, dormant DTCs must integrate survival mechanisms to remain viable for long periods of time. Here, the pro-survival role of autophagy in tumor cell dissemination and dormant DTC maintenance are discussed, as well as the implications of the current knowledge for future research efforts.