Seizing Cancer Completely Through Specific Ablating Cancer Stem Cell: The Royal Road to Chemoquiescence

Abstract

Cellular quiescence is defined with reversible nonproliferating state and featured with a low metabolic state such as decreased glycolysis, reduced translation rates, and activation of autophagy. As signal for quiescence or dormancy, reduced cell growth and biosynthesis inactivating the TOR kinase are essential, but cellular quiescence is not always associated with reduced metabolism since it is also possible to achieve a state of cellular quiescence in which glucose uptake, glycolysis, and flux through central carbon metabolism are not reduced. However, in contrast to normal cells, cancer cells, especially cancer stem or dormancy cells, intrinsic and acquired resistance led to resistance to cancer therapeutics, but can be reversed with the acquisition of chemoquiescence. The development of new drug combinations or strategy to treat the highly aggressive and metastatic cancers including relapsed leukemias, melanoma, and head and neck, brain, lung, breast, ovary, prostate, pancreas as well as gastrointestinal cancers can be feasible with the combination of chemoquiescence agent, in which cancer stem cells (CSCs) or tumor dormancy can be possibly eradicated or removed. Therefore, active investigations of metformin or chloroquine as well as other drugs under revisited study, such as potassium channel-inhibiting acid pump antagonist, sonic hedgehog inhibitors, and Akt inhibitor, are actively performing under the hopeful vision of chemoquiescence, aiming at achieving complete cancer cure as well as prevention of cancer recurrence far beyond the scope of current chemotherapy or chemoprevention. In this chapter, the evolving concept of chemoquiescence or cancer dormancy will be introduced accompanied by introduction of some novel drug development targeted for chemoquiescence. Now, we should seize as well as eradicate rotten root of cancer for cure.