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the level of cytogenetic visibility, a decrease that is still ongoing in many patients 15
months after attainment of a complete cytogenetic remission with imatinib treat-
ment. Moreover, patients who attained such a molecularly defi ned minimal tumor
burden had a higher rate of progression-free survival than those who did not. The
molecular data thus provide support for the position of imatinib as the drug of
choice in CML.
DNA Repair Biomarkers
Most chemotherapeutics and radiation therapy work by damaging DNA. All solid
cancers have multiple pathways and some of these can enable tumor cells to survive
DNA damage induced by chemotherapeutic treatments. Therefore, inhibitors of
specifi c DNA repair pathways might prove effective when used in combination with
DNA-damaging chemotherapeutic drugs. In addition, alterations in DNA repair
pathways that arise during tumor development can make some cancer cells reliant
on a reduced set of DNA repair pathways for survival. There is evidence that drugs
that inhibit one of these pathways in such tumors could prove useful as single-agent
therapies, with the potential advantage that this approach could be selective for
tumor cells and have fewer side effects (Helleday et al. 2008 ). Proteomic biomark-
ers in each of the pathways differ according to the type of cancer but they overlap.
Since most available cancer therapeutics work by inducing DNA damage, which
causes cell death, monitoring specifi c DNA repair biomarkers may indicate whether
the therapeutic is producing tumor cell death. DNA repair biomarkers could enable
physicians to monitor treatment effectiveness from solid tumor samples.
Fluorescent In Situ Hybridization
Fluorescence in situ hybridization (FISH) is now used routinely in the clinical labo-
ratory during all phases of management of a number of malignancies. The specifi c
associations between distinct chromosomal abnormalities and different types of
cancers will necessitate simultaneous detection of multiple abnormalities using
multicolor/multiplex FISH tests more often in the near future and will bring the
concept of personalized medicine in cancer closer to reality than ever before.
Gene Expression Profi ling
Aberrant expression of p53, myc, and ras is known to initiate tumorigenesis and
progression of tumors. p53 mutations are associated with drug resistance and treat-
ment failure while activation of oncogenes c-myc and ras is often associated with
10 Personalized Therapy of Cancer