Version 1
: Received: 23 September 2021 / Approved: 24 September 2021 / Online: 24 September 2021 (12:44:34 CEST)
How to cite:
Saxena, K.; Subbalakshmi, A.R.; Kulkarni, P.; Jolly, M.K. Cancer: More Than a Geneticist’s Pandora’s Box. Preprints2021, 2021090432. https://doi.org/10.20944/preprints202109.0432.v1
Saxena, K.; Subbalakshmi, A.R.; Kulkarni, P.; Jolly, M.K. Cancer: More Than a Geneticist’s Pandora’s Box. Preprints 2021, 2021090432. https://doi.org/10.20944/preprints202109.0432.v1
Saxena, K.; Subbalakshmi, A.R.; Kulkarni, P.; Jolly, M.K. Cancer: More Than a Geneticist’s Pandora’s Box. Preprints2021, 2021090432. https://doi.org/10.20944/preprints202109.0432.v1
APA Style
Saxena, K., Subbalakshmi, A.R., Kulkarni, P., & Jolly, M.K. (2021). Cancer: More Than a Geneticist’s Pandora’s Box. Preprints. https://doi.org/10.20944/preprints202109.0432.v1
Chicago/Turabian Style
Saxena, K., Prakash Kulkarni and Mohit Kumar Jolly. 2021 "Cancer: More Than a Geneticist’s Pandora’s Box" Preprints. https://doi.org/10.20944/preprints202109.0432.v1
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 modelling and in vitro/in vivo experiments can map the diverse phenotypic repertoire, and identify therapeutic vulnerabilities of an otherwise clonal cell population.
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
