Posted by: Dan | November 18, 2006

Evolving Ecosystem Model of Cancer in NRC

I’ve discussed the evolving ecosystem model of neoplasms, previously, but now Nature Reviews Cancer has a noteworthy and thorough review on the theory by Merlo et al. The bulleted summary:

  • Neoplasms are composed of an ecosystem of evolving clones, competing and cooperating with each other and other cells in their microenvironment, and this has important implications for both neoplastic progression and therapy.
  • Selection at the different levels of genes, cells and organisms might conflict, and have resulted in a legacy of tumour-suppression mechanisms and vulnerability to oncogenesis in our genomes.
  • Most of the dynamics of evolution have not been measured in neoplasms, including mutation rates, fitness effects of mutations, generation times, population structure, the frequency of selective sweeps and the selective effects of our therapies.
  • Many of the genetic and epigenetic alterations observed in neoplasms are evolutionarily neutral.
  • Cancer therapies select for cancer stem cells with resistance mutations, although various evolutionary approaches have been suggested to overcome this problem, including selecting for benign or chemosensitive cells, altering the carrying capacity of the neoplasm and the competitive effects of neoplastic and normal cells on each other.
  • Dispersal theory suggests that high cell mortality and variation of resources and population densities across space might select for metastasis.
  • There is evidence of competition, predation, parasitism and mutualism between co-evolving clones in and around a neoplasm.
  • We will need to interfere with clonal evolution and alter the fitness landscapes of neoplastic cells to prevent or cure cancer. Evolutionary biology should be central to this endeavor.

It’s really well-written, and I’m sure that it will be as much of a classic as Hanahan and Weinberg’s 2000 review in Cell: The hallmarks of cancer.

More on Merlo et al. in ScienceDaily.

Reference:

  • Merlo LM, Pepper JW, Reid BJ, Maley CC. Cancer as an evolutionary and ecological process. Nat Rev Cancer. 2006 Nov 16; [Epub ahead of print]. Pubmed.
  • Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70. Pubmed.

Responses

  1. […] self-renewal and clonal expansion in cancer cells. Indeed, this description fits better with the evolving ecosystem model of cancer than the stem cell model. That said, yes, pathways mediating self-renewal and proliferative […]

  2. […] A merger of Hanahan & Weinberg’s model (2000) of trait acquisition in cancer progression and Merlo et al.’s (2006) model of an evolving neoplastic ecosystem fit the collective data much better, as I’ve said before. […]


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