The origins of cancer cell dormancy

Abstract

Cancer cell dormancy has emerged as an important nongenetic driver of drug resistance. Dormant cells are characterized by a reversible cell cycle exit. They represent a reservoir for eventual cancer relapse, and upon reactivation, can fuel metastatic disease. Although dormant cells were originally believed to emerge from a drug-resistant pre-existing cancer subpopulation, this notion has been recently challenged. Here, we review recent evidence indicating that dormancy represents an adaptive strategy employed by cancer cells to avoid the cytotoxic effects of antitumor therapy. Furthermore, we outline the molecular pathways engaged by cancer cells to enter dormancy upon drug exposure, with a focus on cellular senescence as a driver of dormancy.

Figure 1.. Dormancy as an adaptive strategy for cancer cells during a time of stress to fuel cancer relapse.

Anti-cancer drug treatment induces a transition from a proliferative state to a dormant state in cancer cells that exhibit some predisposition at the time of drug exposure. Molecular mechanisms with overlapping features such as quiescence, diapause and senescence have emerged as the pathways responsible for the lack of proliferation that characterizes dormancy. Dormant cells remain viable for years or decades and can disseminate to secondary sites where upon receiving reactivating cues, such as chronic inflammation or TGFβ1 signaling, they start proliferating again and give rise to new tumors.