Cancer: More than a geneticist’s Pandora’s box

Saxena, K and Subbalakshmi, AR and Kulkarni, P and Jolly, MK (2022) Cancer: More than a geneticist’s Pandora’s box. In: Journal of Biosciences, 47 (2).

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Abstract

Despite identical genetic constitution, a cancer cell population can exhibit phenotypic variations termed as non-genetic/non-mutational heterogeneity. Such heterogeneity – a ubiquitous nature of biological systems – has been implicated in metastasis, therapy resistance and tumour relapse. Here, we review the evidence for existence, sources and implications of non-genetic heterogeneity in multiple cancer types. Stochasticity/noise in transcription, protein conformation and/or external microenvironment can underlie such heterogeneity. Moreover, the existence of multiple possible cell states (phenotypes) as a consequence of the emergent dynamics of gene regulatory networks may enable reversible cell-state transitions (phenotypic plasticity) that can facilitate adaptive drug resistance and higher metastatic fitness. Finally, we highlight how computational and mathematical models can drive a better understanding of non-genetic heterogeneity and how a systems-level approach integrating mathematical modeling and in vitro/in vivo experiments can map the diverse phenotypic repertoire and identify therapeutic vulnerabilities of an otherwise clonal cell population. © 2022, Indian Academy of Sciences.

Item Type:	Journal Article
Publication:	Journal of Biosciences
Publisher:	Springer
Additional Information:	The copyright for this article belongs to Springer
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	17 May 2022 09:28
Last Modified:	17 May 2022 09:28
URI:	https://eprints.iisc.ac.in/id/eprint/71740

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