Chemoquiescence for Ideal Cancer Treatment and Prevention: Where Are We Now?

Abstract

Cellular quiescence is a state of reversible cell cycle arrest and is associated with a low metabolic state featured with decreased glycolysis, reduced translation rates, and activation of autophagy, fundamentally to provide nutrients for cell survival similar as seen in hybernation. As signal for quiescence, inactivating the target of rapamycin kinase and resulting reduced cell growth and biosynthesis 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 cancer cells, overcoming intrinsic and acquired resistance of cancer stem or cancer dormancy cells to current clinical treatments can be reversed with the acquisition of chemoquiesence. The development of new drug combinations or strategy to treat the highly aggressive and metastatic cancers including relapsed leukaemias, melanoma and head and neck, brain, lung, breast, ovary, prostate, pancreas as well as gastrointestinal cancers which remain incurable in the clinic in spite of aggressive therapies, can be accelerated with the introduction of chemoquiescence agent, for which cancer stem cells or tumor dormancy should be eradicated or removed. Recently potential applications of metformin or chloroquine as well as the potential drugs under investigation such as proton pump inhibitor, sonic hedgehog inhibitor, and Akt inhibitor, are actively investigated in this field of chemoquiescence to achieve cancer cure far beyond those of chemoprevention. In this review article, the evolving concept of chemoquiescence or cancer dormancy will be introduced accompanied by a description of novel target drug development.

AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects

“…[23][24][25][26][27][28] Rapamycin, for example, is a potent candidate to trigger autophagic activity in patients diagnosed for different types of cancer. 29,30 However, this compound enhances autophagy by blocking the MTOR (mechanistic target of rapamycin, [serine/threonine kinase]) kinase system, which in turn affects translation. Perturbation of general protein synthesis is certainly not a desired purpose in medical applications.…”

A platform for high-throughput bioenergy production phenotype characterization in single cells

“…In all three cases our data revealed subpopulations of cells with slow OCR and ECAR in both control and treated cells. While further studies are necessary to reveal the functional role of these cells at the population and tissue level, it is possible that due to their dormant-like metabolic phenotype behavior these cells may play a role in drug response and cancer recurrence after treatment3132.…”

Cancer Stem Cells and Cancer Stem Cell Inhibitors in Gastrointestinal Cancers

“…This is a state of reversible cell cycle arrest, associated with reduced translation rate, activation of autophagy, and a low metabolic rate as characterized by decreased glycolysis. 86 This is a burgeoning area of research and it has been suggested that the efficacy of CSC inhibitors and conventional therapies may be enhanced if used in combination with chemoquiescence-inducing agents such as chloroquine and its analogues.…”