Scientists identify two new key players involved in development of prostate cancer

Understanding how a normal healthy cell turns into a cancerous one is our best bet yet for beating the disease. It will help better diagnose the cancer type, and enable the development of more effective, and less toxic therapies. But cells have evolved all sorts of sophisticated ways to become cancerous, and identifying the molecules involved and how they function in each type of cancer is a major undertaking. New research published in the Proceedings of the National Academy of Sciences has provided a major boost for the prostate cancer field by uncovering an unprecedented mechanism for developing cancer.

Doctors and scientists at the University of New Mexico Cancer Center are among the authors of the research paper. The multidisciplinary team identified two new key players in the development of prostate cancer, which is the second most common malignancy in men and can become highly aggressive. The two players, PCA3 and PRUNE2, unusually come from the same location in the genome. They also physically interact and regulate each other's activity. "It's a completely new regulatory system," says Renata Pasqualini, PhD, senior co-author of the paper. Pasqualini and her husband, Wadih Arap, MD, PhD, are prostate cancer experts and led the research team. "We have shown in animals that if we lower PCA3 [in the prostate cells] the animals develop smaller tumors," says Arap. "If we increase PRUNE2, they develop smaller tumors; indeed, it is the first time that a function for the FDA-approved, clinically-used PCA3 biomarker was discovered."

Dr. Webster K. Cavenee, the Director of the Ludwig Institute for Cancer Research and Distinguished Professor of Medicine at the University of California-San Diego, who is also a collaborator and senior co-author of the PNAS manuscript remarked that the work "essentially enables the first understanding of molecular mechanisms related to the PCA3/PRUNE2 axis in the development of human prostate cancer, which may well lead to more accurate diagnoses and more appropriate application of therapy in patients with this malignant tumor." Emmanuel Dias-Neto, PhD, senior co-author of the paper and genomics expert at A.C. Camargo Cancer Center in São Paulo, Brazil agrees. "The definition of the PCA3 role in prostate cancer adds value to its importance as diagnostic marker but, more importantly, it opens up new therapeutic avenues," notes Dias-Neto. "Now, not only can PCA3 be a target of an anti-prostate cancer drug, but also PRUNE2, P54 and ADAR1 can be valuable for the design of new therapeutic strategies."

The work is still in its early stages, cautions Richard Lauer, MD, FACP. Lauer is among the authors and is an expert in cancers of the prostate, bladder and kidney. But the potential to help patients is there. "PRUNE2 may prevent the development of prostate cancer," Lauer says. "PCA3 down regulates it so if that access can be manipulated, it may be important therapeutically."