Textbook of Personalized Medicine - Second Edition [2015]

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prostatectomy. Because the patient outcome depends on the level of PSA, this
ultrasensitive assay enables: (1) informing patients, who have undetectable PSA lev-
els with conventional assays, but detectable and nonrising levels with the barcode
assay, that their cancer will not recur; (2) earlier detection of recurrence earlier
because of the ability to measure increasing levels of PSA before conventional tools
can make such assignments; and (3) use of PSA levels, which would otherwise not be
detectable with conventional assays, to follow the response of patients to treatment.


Effects of Lifestyle Changes Shown by Gene Expression Studies


Epidemiological and prospective studies indicate that comprehensive lifestyle
changes may modify the progression of prostate cancer. A pilot study was con-
ducted to examine changes in prostate gene expression in a unique population of
men with low-risk prostate cancer who declined immediate surgery, hormonal ther-
apy, or radiation and participated in an intensive nutrition and lifestyle intervention
while undergoing careful surveillance for tumor progression (Ornish et al. 2008 ).
Consistent with previous studies, signifi cant improvements in weight, abdominal
obesity, blood pressure, and lipid profi le were observed. Gene expression profi les
were obtained from RNA samples from control prostate needle biopsy taken before
intervention to RNA from the same patient’s 3-month postintervention biopsy.
Quantitative real-time PCR was used to validate array observations for selected
transcripts. Two-class paired analysis of global gene expression using signifi cance
analysis of microarrays detected 48 up-regulated and 453 down-regulated tran-
scripts after the intervention. Pathway analysis identifi ed signifi cant modulation of
biological processes that have critical roles in tumorigenesis, including protein
metabolism and modifi cation, intracellular protein traffi c, and protein phosphoryla-
tion. Intensive nutrition and lifestyle changes may modulate gene expression in the
prostate. Understanding the prostate molecular response to comprehensive lifestyle
changes may strengthen efforts to develop effective prevention and treatment. The
study not only provides insights into potential drug targets, but also suggests that
lifestyle changes could produce benefi ts akin to therapeutic interventions. Larger
clinical trials are warranted to confi rm the results of this pilot study.


Prolaris Assay for Determining Prognosis in Prostate Cancer


Prolaris test (Myriad) quantifi es a patient’s risk of disease progression and prostate
cancer specifi c mortality using a gene-expression-based cell cycle progression
(CCP) score. A prospective study found that CCP score adds meaningful new infor-
mation to risk assessment for localized prostate cancer patients (Shore et al. 2014 ).
Use of the test in practice is likely to have an impact on the management in a signifi -
cant portion of tested patients, particularly by shifting the trend towards more con-
servative management. This could reduce overtreatment of patients with less
aggressive disease, decreasing patient morbidity and costs for payers and the health-
care system.


Personalized Management of Cancers of Various Organs

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