Textbook of Personalized Medicine - Second Edition [2015]

(Ron) #1

360


routine contrast-enhanced CT scans of individual human PDAC tumors (Koay et al.
2014 ). Additionally, gemcitabine infusion during PDAC resection was evaluated in
patients, measuring gemcitabine incorporation into tumor DNA and correlating its
uptake with human equilibrative nucleoside transporter (hENT1) levels, stromal
reaction, and CT-derived mass transport properties. Study of associations between
CT-derived transport properties and clinical outcomes in patients who received pre-
operative gemcitabine-based chemoradiotherapy for resectable PDAC revealed
striking differences in transport properties between normal pancreas and the tumor.
Refl ecting the interpatient differences in contrast enhancement, resected tumors
exhibited dramatic differences in gemcitabine DNA incorporation, despite similar
intravascular pharmacokinetics. Gemcitabine incorporation into tumor DNA was
inversely related to CT-derived transport parameters and PDAC stromal score, after
accounting for hENT1 levels. Moreover, stromal score directly correlated with
CT-derived parameters. Among patients who received preoperative gemcitabine-
based chemoradiotherapy, CT-derived parameters correlated with pathological
response and survival. It was concluded that gemcitabine incorporation into tumor
DNA is highly variable and correlates with multiscale transport properties that can
be derived from routine CT scans. Furthermore, pretherapy CT-derived properties
correlate with clinically relevant endpoints. The study introduces and strongly sup-
ports the concept of quantitative biophysical markers that may provide clinically
useful data to help direct personalized cancer treatment and thereby improve the
survival of patients with PDAC and other solid tumors.


Personalized Management of Prostate Cancer


Prostate cancer is the most common type of cancer found in American men, other
than skin cancer, and is the second leading cause of cancer deaths, according to the
American Cancer Society. Over 240,000 men are diagnosed with prostate cancer in
the US every year. Research is aimed at fi nding gene variants associated with sus-
ceptibility to cancer. Molecular diagnostics has been used to guide therapy of pros-
tate cancer.


Assessing Susceptibility to Prostate Cancer by Genotyping


The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility.
High resolution fi ne-mapping analysis has been performed to comprehensively
evaluate the association between common genetic variation across the HOXB
genetic locus at 17q21 and PrCa risk (Saunders et al. 2014 ). This involved genotyp-
ing 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputa-
tion of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL
consortium. The study identifi ed a cluster of highly correlated common variants
situated within or closely upstream of HOXB13 that were signifi cantly associated


10 Personalized Therapy of Cancer
Free download pdf