A Double-Blind, Randomised, Placebo-Controlled Study of the Effect of Transdermal Nitroglycerin (Glyceryl Trinitrate; GTN) Therapy on Biomarkers of Immune Escape in Men With Biochemical Recurrence of Prostate Cancer After Primary Therapy
Prostate cancer is the most commonly diagnosed cancer in men in Canada. Over 30% of men over
the age of fifty have histological evidence of prostate cancer on biopsy. Despite the stage
migration afforded by early detection with serum prostate specific antigen (PSA) testing and
an apparent trend toward improved survival over the past several years, prostate cancer
remains a significant cause of morbidity and mortality. Biochemical failure after primary
therapy (surgery or radiation) remains a significant health care burden and strategies to
delay clinical prostate cancer progression and prolong the interval from treatment failure
to systemic therapy would be of significant clinical benefit for those men suffering from a
finding of PSA recurrence.
PSA is widely accepted as the most useful prognostic marker of prostate cancer progression,
particularly after primary therapy with radical surgery or radiation. 5 Despite improved
cancer control rates with definitive management of early stage prostate cancer, a PSA
recurrence is unfortunately a common occurrence (25-50%) in most large case series.
Microenvironmental factors have been demonstrated to play a pivotal role in the selection of
neoplastic cell subpopulations expressing more malignant phenotypes and contributing to the
progression of localized and metastatic disease. Very low levels of O2 (< 10 mmHg) has been
well described in many solid tumours (including prostate cancer) and the extent of hypoxia
has been demonstrated to represent an independent marker of a poor prognosis for patients
with various types of cancers. Tumour hypoxia contributes to numerous adaptive phenotypes
including increased invasion and metastasis, as well as evasion of immune cell surveillance
increased resistance to radiation therapy and chemotherapy. Although cellular adaptive responses
to hypoxia are likely mediated by various mechanisms, our previous preclinical studies
suggest that decreased nitric oxide (NO)-dependent signalling plays a significant role in
this progression of a malignant phenotype.
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