Areas low in oxygen correlate with a rise in PSA levels, a marker of tumor recurrence.

Researchers at the Fox Chase Cancer Center have discovered that low-oxygen regions called hypoxia in prostate tumors can be used to project the recurrence of cancer. The team had published six previous research papers between 2000 and 2002 detailing a link between hypoxia, radio resistance, and the risk of increased prostate-specific antigen (PSA) levels.

But in the current research, to be presented May 31 at the 2009 American Society of Clinical Oncology annual meeting, the team has more mature data, and has increased the median follow-up from 19 months to 8 years. The rise in PSA levels are a marker of tumor recurrence in prostate cancer.

The investigators used a custom-built probe to monitor the amount of oxygen that prostate tumors and noncancerous muscle tissue were receiving. The probe was used on 57 patients with low or intermediate risk of cancer just before the patients received a form of localized radiation therapy. The team then tracked the patients over time, looking for a correlation between the amount of oxygen levels in the prostate tumor relative to the muscle tissue at the time of therapy. The researchers later looked at the increase in PSA levels.

Eight of the 57 patients experienced an increase in PSA levels following prostate cancer treatment. Overall, average muscle oxygenation was 12.5 times higher than that of the tumor (30 mm Hg vs. 2.4 mm Hg). Using a statistical model that accounted for such risk factors as tumor grade, PSA level, and tumor size, the team determined that hypoxia was a significant independent predictor of an increase in PSA levels.

Now the group is developing noninvasive screening methods to identify hypoxic tumors, and more potent anticancer weapons to target them. “We already knew that there are hypoxic regions within cancers,” said Aruna Turaka, M.D., radiation oncology fellow at Fox Chase and lead author on the study. “The future goal is to interpolate that to relate to the expression of molecular markers [such as hypoxia-inducible factor-1-alpha] and attack those tumors with dose-escalation radiation oncology strategies and targeted agents.”

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