261cell death in both cancer cells and normal cells engineered to have a cancer genotype,
irrespective of p53 status, but it has little effect on normal cells. Signifi cant antitu-
mor effects were observed in mouse xenograft tumor models treated with piper-
longumine, but no toxic effects were observed in normal mice. Moreover,
piperlongumine inhibits the growth of spontaneous breast cancers in mice. These
fi ndings show that ability a small molecule can selectively induce apoptosis in cells
that have a cancer genotype by targeting a non-oncogene dependency acquired
through the expression of the cancer genotype in response to oxidative stress
induced by malignant transformation.
Targeting Enzymes to Prevent Proliferation of Cancer Cells
CFI-400945 has been designed by a team of scientists in the Canada and China to
specifi cally prevent proliferation of cancer cells but not damage normal cells. It
targets an enzyme called PLK4, which plays a critical role in cell division, espe-
cially in cancer cells. Cells in genomically unstable cancers can have scores more
chromosomes than the 46 present in normal cells, and these malignant cells rely on
PLK4 to be able to continue to proliferate out of control. Targeting this enzyme
would prevent survival of these cells. Animal experimental studies have been com-
pleted and FDA permission to start human clinical trials is pending with expected
go ahead in the fall of 2013. Initial trial with the drug will be a study in patients with
breast or ovarian cancers to determine a safe dose.
Role of Oncoproteomics in Personalized Therapy of Cancer
Clinical proteomics is an exciting new subdiscipline of proteomics that involves the
application of proteomic technologies at the bedside, and cancer, in particular, is a
model disease for studying such applications. Oncoproteomics is the term used for
application of proteomic technologies in oncology. Proteomic technologies are
being developed to detect cancer earlier, to discover the next generation of targets
and imaging biomarkers, and to tailor the therapy to the patient. Proteomic tech-
nologies will be used to design rational drugs according to the molecular profi le of
the cancer cell and thus facilitate the development of personalized cancer therapy.
Proteomic separation and analytical techniques are uniquely capable of detecting
tumor-specifi c alterations in proteins.
Cancer Tissue Proteomics
Cancer tissue proteomics implies direct tissue profi ling and use of imaging MALDI
MS to provide a molecular assessment of numerous expressed proteins within a tis-
sue sample. Analysis of thin tissue sections results in the visualization of 500–1,000
Role of Oncoproteomics in Personalized Therapy of Cancer