Evolutionary Dynamics Unifies Carcinogenesis and Cancer Therapy
By Robert James Gillies, Daniel Verduzco, Robert A. Gatenby. Nature Reviews. Cancer, 2012
625 citations recorded by the source corpus.
All malignant cancers, whether inherited or sporadic, are fundamentally governed by Darwinian dynamics. The process of carcinogenesis requires genetic instability and highly selective local microenvironments, the combination of which promotes somatic evolution. These microenvironmental forces, specifically hypoxia, acidosis and reactive oxygen species, are not only highly selective, but are also able to induce genetic instability. As a result, malignant cancers are dynamically evolving clades of cells living in distinct microhabitats that almost certainly ensure the emergence of therapy-resistant populations. Cytotoxic cancer therapies also impose intense evolutionary selection pressures on the surviving cells and thus increase the evolutionary rate. Importantly, the principles of Darwinian dynamics also embody fundamental principles that can illuminate strategies for the successful management of cancer.
Subfields: Cancer Research, Cell Biology, Modeling and Simulation
View Paper: https://www.semanticscholar.org/paper/d1951d018faa4c4daefe712742a1e85e4f57669a
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
In Cell Biology
In Modeling and Simulation
Citations in the corpus
- Immunogenic cell death and DAMPs in cancer therapy (2012, background): “These authors showed that a recombinant N-terminal fragment of CRT (39-272) is a potent inducer of activation and maturation of B cells and macrophages and can trigger Ig class switching in B cells without T cell help in vitro and in vivo72.”
- Intratumor heterogeneity: evolution through space and time. (2012, background): “For these reasons, some rightly argue that focusing on the consequences of genetic diversity in terms of common tumor phenotypes, rather than the specific genetic aberrations themselves, may prove more beneficial (27).”
- Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “Given the well documented impact of hypoxia, acidity, and nutrient status on therapy sensitivity (Gillies et al., 2012), metabolic microenvironmental heterogeneity likely provides an important modulator of tumor responses to therapies, a notion supported by in silico modeling (Robertson-Tessi et al.”
- Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front (2019, background): “of the iTME, and considerable local and regional variability are observed within individual tumors and in the surrounding tissue (Gillies et al., 2012; Junttila and de Sauvage, 2013).”