Clonal evolution in cancer. Nature

Division of Molecular Pathology, The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK.
Nature (Impact Factor: 42.35). 01/2012; 481(7381):306-13. DOI: 10.1038/nature10762
Source: PubMed

ABSTRACT Cancers evolve by a reiterative process of clonal expansion, genetic diversification and clonal selection within the adaptive landscapes of tissue ecosystems. The dynamics are complex, with highly variable patterns of genetic diversity and resulting clonal architecture. Therapeutic intervention may destroy cancer clones and erode their habitats, but it can also inadvertently provide a potent selective pressure for the expansion of resistant variants. The inherently Darwinian character of cancer is the primary reason for this therapeutic failure, but it may also hold the key to more effective control.

Download full-text


Available from: Carlo Maley, Mar 24, 2015
    • "The stochastic (clonal evolution) model states that every cell within a tumor has similar tumorigenic and selfrenewing potential. These cells evolve and lead to heterogeneity , through clonal expansion with acquired genetic and epigenetic changes over time (Nowell, 1976; Shackleton et al., 2009; Greaves and Maley, 2012). This process is influenced by extrinsic factors including therapies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30-90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer treatments, and how this approach can be applied as an alternative option to combat melanoma, and overcome melanoma relapse or resistance in current treatment regimens.Journal of Investigative Dermatology advance online publication, 7 May 2015; doi:10.1038/jid.2015.145.
    Journal of Investigative Dermatology 05/2015; DOI:10.1038/jid.2015.145 · 6.37 Impact Factor
  • Source
    • "In this case, the change from a primary cancer to a metastatic or relapsing state implies an evolutionary selection, since some specic steps need to occur, e.g. regarding epythelial-to-mesenchymal transition mechanisms [23] or adaptation to pharmacoresistance [24], or clonal selection induced by therapy [25]. "
    Molecular BioSystems 04/2015; DOI:10.1039/C5MB00143A · 3.18 Impact Factor
  • Source
    • "This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications. Keywords Adaptationism, Cancer, Evolutionary processes Following the pioneer works of Cairns (1975) and Nowell (1976), cancer is perceived as a phenomenon whose origins and dynamics result from evolutionary processes (Cairns 1975; Nowell 1976; Merlo et al. 2006; Greaves and Maley 2012; Thomas et al. 2013). Placing cancer in an evolutionary ecology landscape is not a semantic problem, but rather a necessity to understand the origins and progression of cancer with the ultimate aim of developing ways to control neoplastic progression and, most importantly, to prevent cancer and improve therapy when cancer occurs (Aktipis and Nesse 2013; Thomas et al. 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The evolutionary perspective of cancer (which origins and dynamics result from evolutionary processes) has gained significant international recognition over the past decade, and generated a wave of enthusiasm among researchers. In this context, several authors proposed that insights in evolutionary and adaptation dynamics of cancers can be gained by studying the evolutionary strategies of organisms. Although this reasoning is fundamentally correct, in our opinion it contains a potential risk of excessive adaptationism, potentially leading to the suggestion of complex adaptations that are unlikely to evolve among cancerous cells. For example, the ability of recognizing related conspecifics and adjusting accordingly behaviors as in certain free-living species, appears unlikely in cancer. Indeed, despite their rapid evolutionary rate, malignant cells are under selective pressures for their altered lifestyle for only few decades. In addition, even though cancer cells can theoretically display highly sophisticated adaptive responses, it would be crucial to determine the frequency of their occurrence in cancer patients, before therapeutic applications can be considered. Scientists who try to explain oncogenesis will need in the future to critically evaluate the metaphorical comparison of selective processes affecting cancerous cells with those affecting organisms. This approach seems essential for the applications of evolutionary biology to understand the origin of cancers, with prophylactic and therapeutic applications.This article is protected by copyright. All rights reserved.
    Evolutionary Applications 04/2015; 8(6). DOI:10.1111/eva.12265 · 4.57 Impact Factor
Show more