Journal
JOURNAL OF MOLECULAR MEDICINE-JMM
Volume 98, Issue 2, Pages 161-177Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-020-01874-2
Keywords
Intratumor heterogeneity; Liquid biopsy; Artificial intelligence; Antitumor therapeutics
Funding
- Fondo de Investigaciones Sanitarias [PI14/01320, PI17/02247]
- Redes Tematicas de Investigacion Cooperativa en Salud [RD12/0036/0057]
- CIBERONC [CB16/12/00363]
- Generalitat de Catalunya (AGAUR) [2017 SGR 1799, 2014 SGR 1131]
- Instituto de Salud Carlos III [PI16/00772, CPII16/00042]
- European Regional Development Fund (ERDF)
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In this review, we highlight the role of intratumoral heterogeneity, focusing on the clinical and biological ramifications this phenomenon poses. Intratumoral heterogeneity arises through complex genetic, epigenetic, and protein modifications that drive phenotypic selection in response to environmental pressures. Functionally, heterogeneity provides tumors with significant adaptability. This ranges from mutual beneficial cooperation between cells, which nurture features such as growth and metastasis, to the narrow escape and survival of clonal cell populations that have adapted to thrive under specific conditions such as hypoxia or chemotherapy. These dynamic intercellular interplays are guided by a Darwinian selection landscape between clonal tumor cell populations and the tumor microenvironment. Understanding the involved drivers and functional consequences of such tumor heterogeneity is challenging but also promises to provide novel insight needed to confront the problem of therapeutic resistance in tumors.
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