Textbook of Personalized Medicine - Second Edition [2015]

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randomized phase II trial using docetaxel and thalidomide versus docetaxel alone
were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1,256
genetic variations in 170 drug disposition genes (Deeken et al. 2010 ). Genetic poly-
morphisms were analyzed for associations with clinical response and toxicity. In
all, 10 SNPs in three genes were potentially associated with response to therapy:
peroxisome proliferator-activated receptor-δ (PPAR-δ), sulfotransferase family,
cytosolic, 1C, member 2 (SULT1C2) and carbohydrate (chondroitin 6) sulfotrans-
ferase 3 (CHST3). Genotyping results between drug metabolizing enzymes and
transporters (DMET) and direct sequencing showed >96 % of concordance. These
fi ndings highlight the role that non-CYP450 metabolizing enzymes and transporters
may have in the pharmacology of docetaxel and thalidomide. DMET appears to
offer great promise in this fi eld as a reliable test unveiling genetic variations that
correlated with drug effectiveness and toxicity.


Detection of Prostate Cancer Metastases


Prostate circulating tumor cells (PCTCs) in circulation are shed from either a pri-
mary tumor or metastases, which are directly responsible for most prostate cancer
deaths. Quantifying exfoliated PCTCs may serve as an indicator for the clinical
management of prostate cancer, isolating and removing of PCTCs could poten-
tially reduce prostate cancer metastasis, and culturing and characterizing captured
PCTCs could facilitate the development of personalized treatment options. PSMA,
an established biomarker for prostate cancer, is strongly expressed on prostate
tumor cells associated with high-grade primary, androgen-independent, and meta-
static tumors.
Chemoaffi nity capture with magnetic beads of pre-targeted PCTCs from periph-
eral blood can serve as an effective tool for the detection of metastatic prostate
cancer, monitoring of treatment, and the development of personalized therapy based
on the responsiveness of PCTCs to chemotherapeutic strategies (Wu et al. 2012 ).
MenaCalc™ Prostate (MetaStat Inc) is a diagnostic for prostate cancer to help in
informed decision about whether to undergo radical surgery and risk its dreaded
side effects.


Early Detection of Cancer Recurrence and Guiding Treatment


An automated gold nanoparticle bio-barcode assay probe has been described for the
detection of prostate specifi c antigen (PSA) at 330 fg/mL, along with the results of a
clinical pilot study designed to assess the ability of the assay to detect PSA in the
serum of 18 men who have undergone radical prostatectomy for prostate cancer
(Thaxton et al. 2009 ). Available PSA immunoassays are often not capable of detect-
ing PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA
assay is approximately 300 times more sensitive than commercial immunoassays and
all patients in this study had a measurable serum PSA level after radical


10 Personalized Therapy of Cancer
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