Perspectives on Ergodic Cancer Therapy Derived from Cloning Genome Chaos via In Vivo Rhabdomyosarcoma RA-2 Models: a Narrative Review.

Abstract

This review explores articles concerning the experimental research cycle on genome instability in cell populations of highly malignant recurrent organotropic rhabdomyosarcoma RA- 2 in rats. Clonal analysis and cloning were pivotal components of this research, which relies on the frequency of cells with micronuclei and internuclear bridges to gauge the intensity of chromothripsis and break-fusion-bridge cycles. The efficacy of cloning, determined by these indicators, stemmed from the deliberate isolation of tumor stem cells, yielding clones in which chromothripsis activity and breakage-fusion-bridge cycles were sustained. Notably, it is plausible that the stem cells themselves, progenitors of these clones, harbor dicentric chromosomes and chromosomal fragments, contributing to the formation of "fatal micronuclei" in their karyotype. Cloning based on bridges and micronuclei has proven effective up to a certain threshold (15%-18%), reaffirming the predicted reproductive extinction of malignant cell populations under mutational pressure and genome chaos, as posited by the genetic theory of cell populations. Furthermore, this review highlights the potential of ergodic cancer therapy as a novel therapeutic strategy. Ergodic therapy offers promising prospects for late-stage and terminal malignant tumors, where conventional treatments may fall short due to advanced progression. Furthermore, by "enhancing chromothripsis" through the induction of additional micronuclei and bridges, ergodic cancer therapy seeks to increase genome chaos to a critical threshold, potentially halting malignant progression. This innovative approach presents opportunities to explore new drugs and targets for chromothripsis-based oncotherapy, addressing the pressing need for effective treatments in advanced stages of malignancy.