JERUSALEM--Tumor cells that are not eradicated by chemotherapy or radiotherapy can enter a prolonged dormant state and thus pose a continuous threat of tumor relapse in patients who are seemingly "cured," Eitan Yefenof, PhD, said in an interview with Oncology News International.
Although there is evidence that prostate cancer cells can enter a prolonged quiescent period following therapy, little is known about the mechanism underlying the induction and maintenance of this dormant state.
Dr. Yefenof, of the Lautenberg Center for General and Tumor Immunology, Jerusalem, and his colleagues at the University of Texas Southwestern Medical Center, Dallas, led by Dr. Jonathan Uhr, have taken the first step toward understanding the dormant state in prostate cancer with their project to establish an experimental model of human prostate cancer dormancy in nude mice.
"Very little is known about the biology of dormant tumor cells and the cellular and molecular mechanisms that lead to the dormant state," Dr. Yefenof said. "We are studying them to see what kinds of genetic mutations are causing the dormant state and how the dormant state can be terminated, eradicated, or kept silent for an extended period so as not to evoke clinical manifestations in the host."
Much of what is known about dormant tumor cells comes from work done by Dr. Yefenof when he was a visiting professor at UT Southwestern in 1993. "We developed an experimental model for tumor dormancy using lymphoma cells. We think what we learned about the dormant state from this model can be applied to carcinomas as well."
Dr. Yefenof believes that dormant tumor cells still have a malignant genotype, but receive a growth inhibitor signal from the environment that prevents their proliferation. The dormant cells may suddenly become active if the inhibitory signal is somehow "turned off" or if the cell itself develops "resistance" to the signal.
"If the countermanding signal is removed, the cells will regrow and produce a tumor," Dr. Yefenof said. Alternatively, the dormant cells may acquire an additional mutation that renders them insensitive or resistant to the external signal that had been keeping them under check.