Textbook of Personalized Medicine - Second Edition [2015]

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techniques is creating the scaffolding for the evolving paradigm shift to personalized
cancer therapy (Kurdziel et al. 2008 ). Molecular imaging, also referred to by the
term “virtual biopsy” can provide a more complete systematic picture of the living
tumor, but it is not likely to replace and would rather be complementary to pathol-
ogy, IHC and genomic analysis. However, molecular imaging methods are certainly
complementary to biopsy. The primary advantages of molecular imaging are that it
is nondestructive, non- or minimally invasive and thus easier on patients, permits
the collection of data over time thus enabling post therapy evaluations, and provides
near real-time functional information, and encompasses large volumes of tissue (the
whole body in most case). One drawback of the molecularly targeted approaches is
the expensive development and lack of interest in the pharmaceutical industry to
combine functional imaging with anticancer drugs in development.


Unraveling the Genetic Code of Cancer


A systematic analysis has been carried out for determining the sequence of well-
annotated human protein-coding genes in two common tumor types to identify
genetic alterations in breast and colorectal cancers (Sjoblom et al. 2006 ). Analysis
of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual
tumors accumulate an average of ~90 mutant genes but that only a subset of these
contribute to the neoplastic process. Using stringent criteria to delineate this subset,
the authors identifi ed 189 genes (average of 11 per tumor) that were mutated at
signifi cant frequency. The vast majority of these genes were not known to be geneti-
cally altered in tumors and are predicted to affect a wide range of cellular functions,
including transcription, adhesion, and invasion. These data defi ne the genetic land-
scape of two human cancer types, provide new targets for diagnostic and therapeutic
intervention, and open fertile avenues for basic research in tumor biology. The
mutated genes in breast and colon cancers were almost completely distinct, suggest-
ing very different pathways for the development of each of these cancer types. Each
individual tumor appeared to have a different genetic blueprint, which could explain
why cancers can behave very differently from person to person. The discovery
could also lead to better ways to diagnose cancer in its early, most treatable stages,
and personalized treatments. Maximizing the numbers of targets available for drug
development in a specifi c cancer means that patients will ultimately receive more
personalized, less toxic drugs.


Cancer Prognosis


Molecular diagnostics provide an easier, less invasive way to determine cancer
prognosis. For example, patients with the greatest degree of amplifi cation (in terms
of gene copy numbers) of the N- myc gene in neuroblastoma, a highly malignant


Cancer Prognosis

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