TITLE:
The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines
AUTHORS:
Peter Chin Wan Fung, Regina Kit Chee Kong
KEYWORDS:
Heat Shock Proteins and Heat Shock Factors, mTORC1, 2 Complexes, Mild Hyperthermia, Anti-Cancer Drugs and HSP-Based Anti-Cancer Vaccine, Immunity Cells Trafficking through High Endothelial Venules of Cancer Site, Intrinsic, Extrinsic, FOXO Translocation, and the PERK-CHOP Apoptotic Pathways, Tyrosine Kinase Receptors
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.8 No.11,
November
28,
2017
ABSTRACT: Heat shock proteins (HSPs) serve to correct
proteins’ conformation, send the damaged proteins for degradation (quality
control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes
mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein
kinase-1 (PDK1),
the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated
proteins form a network participating in protein synthesis, bio-energy
generation, signaling for apoptosis with the help of HSPs. A cancer cell
synthesizes proteins at fast rate and needs more HSPs to work on quality
control. Shutting down this network would lead to cell death. Thus inhibitors
of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to
apoptosis—a “passive approach”. On the other hand, HSPs form complexes with
polypeptides characteristic of the cancer cells; on excretion from the cell, they becomes antigens
for the immunity cells, eventually leading to maturation of the cytotoxic T
cells, forming the basic principle of preparing cancer-specific,
person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer
cell and expel its analog to extracellular region, giving the hope to prepare a
non-person-specific vaccine covering a variety of cancers. Activation of
anti-cancer immunity is the “active approach”. On the other hand, mild
hyperthermia, with increase of intracellular HSPs, has been found to activate
the immunity response, and demonstrate anti-cancer effects. There are certain
“mysteries” behind the mechanisms of the active and passive approaches. We
analyze the mechanisms involved and provide explanations to some mysteries. We
also suggest future research to improve our understanding of these two
approaches, in which HSPs play many roles.