The Enigma of cancer resistance to treatment

Abstract

Polyploid giant cancer cells (PGCC) are evaluated by histopathologists for cancer diagnosis, yet their role in cancer is poorly understood. In this essay, we highlight a particular aspect of these cells in relation to genomic self-organisation and transcriptional networks with relevance to treatment resistance. Embodying dynamic restructuring of the genomic network, epigenome and microenvironment, through explorative adaptation in response to sublethal challenge these cells operate at the edge of chaos and order. This state is manifested through oscillations in opposing cell fate pathways, with accelerated senescence coupled to reprogramming and an atavistic shift towards phylogenetically ancient unicellular genetic programmes accessed through bivalent mediator genes. It recapitulates certain unicellular life-cycles in a cancer “life-cycle” which reciprocally connects the somatic  mitotic cell cycle with the germline cycle of the PGCC.