Posted by: Dan | December 5, 2006

Mathematical Modeling of Metastasis and Selection in Tumor Microenvironments

There’s a paper in last week’s issue of Cell that takes aim at alternative models of metastasis from a computational point of view that I’d like to mention briefly. In Tumor Morphology and Phenotypic Evolution Driven by Selective Pressure from the Microenvironment, Anderson et al. examine a list of variables that could impact cancer cell invasiveness. Cell is accepting comments, and Keith at Omics! Omics! has a brief post on the paper as well.

Specifically, Anderson and colleagues interesting findings (from the abstract):

Unexpectedly, the model simulations predict that harsh tumor microenvironment conditions (e.g., hypoxia, heterogenous extracellular matrix) exert a dramatic selective force on the tumor, which grows as an invasive mass with fingering margins, dominated by a few clones with aggressive traits. In contrast, mild microenvironment conditions (e.g., normoxia, homogeneous matrix) allow clones with similar aggressive traits to coexist with less aggressive phenotypes in a heterogeneous tumor mass with smooth, noninvasive margins. Thus, the genetic make-up of a cancer cell may realize its invasive potential through a clonal evolution process driven by definable microenvironmental selective forces. Our mathematical model provides a theoretical/experimental framework to quantitatively characterize this selective pressure for invasion and test ways to eliminate it.

While not resolving the debate between alternative theories of metastasis (e.g. clonal dominance, dynamic heterogeneity, etc.), this paper argues that “invasive tumor properties are reversible under appropriate microenvironment conditions and suggests that differentiating therapy aimed at cancer-microenvironment interactions may be more useful than making the microenvironment harsher (e.g. by chemotherapy or antiangiogenic therapy).”

I don’t know about reversing invasiveness, but it is clear that exploring options other than chemotherapy must be explored for greater efficacy in halting malignancy and progression in cancer. It’s not clear what other options to explore, however – “differentiating therapy,” or therapy custom-tailored to varying genetic profiles for different cancers, will certainly help. And specific pharmacological therapies are already being developed (or in a few cases, have been developed) for some of the primary culprits that could be identified by such screens.

As a model, however, Anderson et al. is useful in that it formally tries to bring together many of these aspects of cancer progression to help reinforce the overall oncological gameplan.

Reference:

  • Tumor Morphology and Phenotypic Evolution Driven by Selective Pressure from the Microenvironment. Alexander R.A. Anderson, Alissa M. Weaver, Peter T. Cummings and Vito Quaranta. Cell, 01 December 2006 127: 905-915.


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