Targeting Cancer Cell Dormancy

HighlightsDormancy is essential for cancer cells to acquire additional mutations, to survive in a new environment and initiate metastasis, to become resistant to cancer therapy, and to evade immune destruction.Dormant cancer cells are considered to be responsible for the progression of primary tumors and metastatic relapse.Cancer cell dormancy is a process whereby cells enter reversible G0 cell cycle arrest.Understanding the mechanisms that enable dormant cell cycle arrest is essential to identifying new pharmacological agents able to target dormant cancer cells.Three distinct strategies aimed to maintain, awaken, or kill dormant cells have been evaluated; however, it remains unclear which strategy would be the most efficacious in the clinic.AbstractCancer cell dormancy is a process whereby cells enter reversible cell cycle arrest, termed quiescence. Quiescence is essential for cancer cells to acquire additional mutations, to survive in a new environment and initiate metastasis, to become resistant to cancer therapy, and to evade immune destruction. Thus, dormant cancer cells are considered to be responsible for cancer progression. As we start to understand the mechanisms that enable quiescence, we can begin to develop pharmacological strategies to target dormant cancer cells. Herein, we summarize the major molecular mechanisms underlying the dormancy of disseminated tumor cells and drug-tolerant persister cells. We then analyze the current pharmacological strategies aimed (i) to keep cancer cells in the harmless dormant state, (ii) to reactivate dormant cells to increase their susceptibility to anti-proliferative drugs, and (iii) to eradicate dormant cancer cells.