The greater genomic landscape: The heterogeneous evolution of cancer

Luay M. Almassalha, Greta M. Bauer, John E. Chandler, Scott Gladstein, Igal Szleifer, Hemant K. Roy, Vadim Backman*

*Corresponding author for this work

Research output: Contribution to journalReview article

14 Scopus citations

Abstract

Results have historically shown a broad plasticity in the origin of tumors and their functions, with significant heterogeneity observed in both morphologies and functional capabilities. Largely unknown, however, are the mechanisms by which these variations occur and how these events influence tumor formation and behavior. Contemporary views on the origin of tumors focus mainly on the role of particular sets of driver transformations, mutational or epigenetic, with the occurrence of the observed heterogeneity as an accidental byproduct of oncogenesis. As such, we present a hypothesis that tumors form due to heterogeneous adaptive selection in response to environmental stress through intrinsic genomic sampling mechanisms. Specifically, we propose that eukaryotic cells intrinsically explore their available genomic information, the greater genomic landscape (GGL), in response to stress under normal conditions, long before the formation of a cancerous lesion. Finally, considering the influence of chromatin heterogeneity on the GGL, we propose a new class of compounds, chromatin-protective therapies (CPT), which target the physical variations in chromatin topology. In this approach, CPTs reduce the overall information space available to limit the formation of tumors or the development of drug-resistant phenotypes.

Original languageEnglish (US)
Pages (from-to)5605-5606
Number of pages2
JournalCancer Research
Volume76
Issue number19
DOIs
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Almassalha, L. M., Bauer, G. M., Chandler, J. E., Gladstein, S., Szleifer, I., Roy, H. K., & Backman, V. (2016). The greater genomic landscape: The heterogeneous evolution of cancer. Cancer Research, 76(19), 5605-5606. https://doi.org/10.1158/0008-5472.CAN-16-0585