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Review
. 2012 Apr;6(2):111-27.
doi: 10.1016/j.molonc.2012.01.011. Epub 2012 Feb 4.

The biology of personalized cancer medicine: facing individual complexities underlying hallmark capabilities

Michele De Palma  1 , Douglas Hanahan
Affiliations
Review

The biology of personalized cancer medicine: facing individual complexities underlying hallmark capabilities

Michele De Palma et al. Mol Oncol. 2012 Apr.

Abstract

It is a time of great promise and expectation for the applications of knowledge about mechanisms of cancer toward more effective and enduring therapies for human disease. Conceptualizations such as the hallmarks of cancer are providing an organizing principle with which to distill and rationalize the abject complexities of cancer phenotypes and genotypes across the spectrum of the human disease. A countervailing reality, however, involves the variable and often transitory responses to most mechanism-based targeted therapies, returning full circle to the complexity, arguing that the unique biology and genetics of a patient's tumor will in the future necessarily need to be incorporated into the decisions about optimal treatment strategies, the frontier of personalized cancer medicine. This perspective highlights considerations, metrics, and methods that may prove instrumental in charting the landscape of evaluating individual tumors so to better inform diagnosis, prognosis, and therapy. Integral to the consideration is remarkable heterogeneity and variability, evidently embedded in cancer cells, but likely also in the cell types composing the supportive and interactive stroma of the tumor microenvironment (e.g., leukocytes and fibroblasts), whose diversity in form, regulation, function, and abundance may prove to rival that of the cancer cells themselves. By comprehensively interrogating both parenchyma and stroma of patients' cancers with a suite of parametric tools, the promise of mechanism-based therapy may truly be realized.

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Figures

Figure 1
Figure 1
Dimensions and key parameters of personalized cancer biology. The complexity and variability of cancer should be interrogated in individual patients. Heterogeneity of both cancer cells (left) and stromal cells (right) can be audited through molecular analysis (including genomics, epigenomics and transcriptomics); immunohistochemistry and flow cytometry; noninvasive imaging; and examination of re‐biopsy specimens obtained from both primary/metastatic tumors and tumor cell exfoliates, before and during treatment, as well as upon treatment failure. The constituent types, relative abundance and dynamics of cancer‐associated leukocytes and fibroblasts (CAFs) should be determined before, during and after treatment; stromal cell signatures may be predictive of patient's prognosis and represent biomarkers of tumor response to therapy. Molecular analysis of whole tumor tissue should be extended to fractionated cancer‐associated stromal cells, including tumor‐derived endothelial cells; molecular signatures comprising single nucleotide polymorphisms (SNPs) and mRNA/miR transcriptomes may be predictive of patient's response to therapy (e.g., antiangiogenic drugs), and thereby provide an encyclopedia of potential new targets of therapy.
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