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(The Cancer Genome Atlas Research Network 2011 ). The equipment used included
Agilent, Illumina, and Affymetrix arrays to look at CNV, mRNA expression,
miRNA expression, and methylation profi les of tumor samples. Whole-exome
sequencing was carried out on a subset of these. High-grade serous ovarian cancer
was found to be characterized by TP53 mutations in almost all tumors. Pathway
analyses suggested that homologous recombination was defective in about half of
the tumors analyzed, and that NOTCH and FOXM1 signaling are involved in serous
ovarian cancer pathophysiology. Although relatively few genes were found to con-
tain recurrent mutations in the ovarian cancer, the researchers tracked down numer-
ous CNVs and several frequently mutated pathways, along with miRNA,
methylation, and transcription signatures that hold promise for categorizing ovarian
cancer and predicting survival outcomes. Overall, these discoveries set the stage for
approaches to the treatment of high-grade serous ovarian cancer in which aberrant
genes or networks are detected and targeted with therapies selected to be effective
against these specifi c aberrations.
Targeting Hematogenous Metastasis of Ovarian Cancer
Ovarian cancer has a clear predilection for metastasis to the omentum, but the
underlying mechanisms involved in ovarian cancer spread were not well under-
stood. A study used OncoCEE microfl uidic device (Biocept Inc), which captures
CTCs and then evaluates the expression of the genomic marker HER3 in ovarian
cancer cells, demonstrated preferential hematogenous metastases of ovarian cancer
to the omentum (Pradeep et al. 2014 ). The study revealed that the ErbB3-neuregulin
1 (NRG1) axis is a dominant pathway responsible for hematogenous omental
metastases. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omen-
tum have enabled tumor cell localization and growth in the omentum. Depletion of
ErbB3 in ovarian cancer impaired omental metastases. These results highlight
hematogenous spread as an important mode of ovarian cancer metastases and use of
this knowledge to design better strategies for prevention and treatment.
V y n fi nit ® for Platinum-Resistant Ovarian Cancer
Platinum-resistant ovarian cancer (PROC) is a challenging disease with a high
unmet need for new treatments. PROC recurs within 6 m of completion of a
platinum- containing regimen, the standard of care for ovarian cancer. An estimated
80 % of platinum-resistant ovarian cancer patients have been found to have folate
receptor-positive disease, and ~40 % express the receptor, as detected by etarfola-
tide, in all of their target tumor lesions. Compared to patients who do not express
folate receptors on their tumors, folate receptor-positive patients have been shown
to have a poorer overall prognosis.
Vintafolide is a conjugate of folic acid (vitamin B9) linked to an anticancer
agent, the potent vinca alkaloid desacetylvinblastine hydrazide. Since cancer cells
10 Personalized Therapy of Cancer