| Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the
development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth,
cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated
molecular programs is far from clear. That is, it is unknown when and which dormant cells will
resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their
hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict
cancer prognosis and may increase the probability of timely therapeutic intervention for the desired
outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms,
including angiogenic switch, immune escape, cancer stem cells, extracellular matrix (ECM) remodeling,
metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced p38 signaling
pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues
to outmaneuver cancer and discuss the implications of such approaches in cancer treatment. |