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ERCC1- XPF as a biomarker in clinical specimens that could help stratify patients
according to cancer risk, response to treatment and overall prognosis (Bhagwat
et al. 2009 ).
Capecitabine (Roche’s Xeloda) is a novel, oral fl uoropyrimidine carbamate ratio-
nally designed to generate 5-fl uorouracil preferentially in tumor tissue via a three-
step enzymatic cascade. It belongs to the category of antimetabolites that stop
cancer cells from making and repairing DNA, which is required for their growth.
Companion diagnostic tests based on various biomarkers − thymidylate synthase,
thymidine phosphorylase, and dihydropyrimidine dehydrogenase − are being inves-
tigated to predict responders to this therapy. Polymorphisms in DNA repair
genes − AREG (amphiregulin) and the ERCC1 (excision repair cross- complementing
group 1) − have been shown as promising predictive biomarkers of response to
capecitabine-based chemoradiotherapy in locally advanced rectal cancer (Sebio
et al. 2015 ).
Ex Vivo Testing of Tumor Biopsy for Chemotherapy Sensitivity
Many oncologists are beginning to believe that new techniques to evaluate tumors’
responses to chemotherapeutic agents promise a future of personalized cancer man-
agement. Rational Therapeutics’ EVA ® assay measures apoptotic events that occur
as a result of drug exposure. Hence, highly responsive cancers are those with the
greatest degree of apoptosis in the laboratory. The Company has developed a novel
regimen for refractory ovarian cancers − gemcitabine plus cisplatin. Study results
showed a correlation between ex vivo sensitivity and resistance and patient out-
come. The Gynecologic Oncology Group, a multicenter non-profi t organization
sponsored by the National Cancer Institute, is conducting a national clinical trial of
the gemcitabine plus cisplatin combination for treatment of relapsed ovarian cancer.
The idea of the assays in predicting chemosensitivity continues to grow. It is not
been used for fi rst-line treatment for ovarian cancer yet because it has not been
proved that anything is more effective than platinum and Taxol. But assays can pro-
vide valuable information for its selection as a second-line treatment. Lack of effi -
cacy of the drug could be due to the drugs’ inability to be delivered to the tumor or
inappropriate levels of drug. In 50–60 % of the instances, a drug is not effective
in vivo even though the in vitro assays predict effi cacy.
ChemoFx Assay (Helomics) is an ex vivo assay designed to predict the sensitiv-
ity and resistance of a given patient’s solid tumor to a variety of chemotherapy
agents (Brower et al. 2008 ). A portion of a patient’s solid tumor, as small as a core
biopsy, is mechanically disaggregated and established in primary culture where
malignant epithelial cells migrate out of tumor explants to form a monolayer.
Cultures are verifi ed as epithelial and exposed to increasing doses of selected che-
motherapeutic agents. The number of live cells remaining post-treatment is enumer-
ated microscopically using automated cell-counting software. The resultant cell
counts in treated wells are compared with those in untreated control wells to
10 Personalized Therapy of Cancer