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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2020; 11(11): 854-867
Published online Nov 24, 2020. doi: 10.5306/wjco.v11.i11.854
Tumor-specific lytic path “hyperploid progression mediated death”: Resolving side effects through targeting retinoblastoma or p53 mutant
Frank-Un Hong, Miguel Castro, Klaus Linse
Frank-Un Hong, Miguel Castro, Klaus Linse, Department of Research and Development, Bio-Synthesis, Lewisville, TX 75057, United States
Author contributions: Hong F has worked on cancer biology, genetics, and pharmacology research; Castro M was involved in therapeutics research; Linse K performed molecular modeling to analyze the 3-dimensional structure of proteins; Hong F, Castro M, and Linse K meet the criteria for authorship established by the International Committee of Medical Journal Editors and verify the validity of the results reported.
Conflict-of-interest statement: Dr. Hong, Dr. Castro, and Dr. Linse have nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Frank-Un Hong, PhD, Research Scientist, Department of Research and Development, Bio-Synthesis, 612 E. Main Street, Lewisville, TX 75057, United States. fhong@coh.org
Received: September 11, 2020
Peer-review started: September 11, 2020
First decision: September 24, 2020
Revised: October 8, 2020
Accepted: October 20, 2020
Article in press: October 20, 2020
Published online: November 24, 2020
Processing time: 67 Days and 22.3 Hours
Abstract

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path “hyperploid progression-mediated death” targeting retinoblastoma (Rb) or p53-mutants defective in G1 DNA damage checkpoint. The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene. It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases. A 3D-structure of Rb dimer is shown, confirming its multimeric status. Rb assumes a central role in cell cycle regulation and the “Rb pathway” is universally inactivated in human cancers. Hyperploidy refers to a state in which cells contain one or more extra chromosomes. Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells. The evidence for the triggering of hyperploid progression-mediated death in RB-mutant human retinoblastoma cells is shown. Hence, the very genetic mutation that predisposes to cancer can be exploited to induce lethality. The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level. By triggering the lytic path, targeted therapy with tumor specificity at the genetic level can be developed. It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.

Keywords: Retinoblastoma protein; P53 protein; Cancer; Checkpoint; Taxol; Tumor-specific lytic path

Core Tip: Side effect remains a major impediment to achieving a cure. An important advance has been made to establish the principle of cytotoxic cancer therapy at the mechanistic level. It concerns the discovery of the tumor-specific lytic path “hyperploid progression mediated death” targeting retinoblastoma (or p53) mutants defective in G1 DNA damage checkpoint. By triggering the lytic path, tumor specificity can be achieved at the genetic level for cytotoxic drugs.