Metastasis, the spread of cancer past the point
of treatment, is what kills men with prostate cancer. Somehow, scientists
must learn how to block metastasis, which is a complicated process, with
many steps. But if metastasis is a railroad track for cancer, maybe scientists
don’t need to dismantle the entire track to derail the train. Maybe
just blocking one section will be enough.
This is what Barry D. Nelkin, Ph.D., professor of oncology, believes,
and he has found a highly promising target — an enzyme called CDK5.
He has been named the Nancy and Jim O’Neal scholar from The Patrick
C.Walsh Prostate Cancer Research Fund to see whether stopping CDK5
will put metastasison hold. Nelkin’s work on this began with a startling
observation: There are “striking similarities” between the
way neuronsmigrate during normal brain development, and the way cancer
cells travel in metastasis.“We reasoned that the underlying mechanisms
of these processes might be similar,”he says. In brain development,
the enzyme CDK5 controls cell migration and invasion. But he
has found that CDK5 is active in the vast majority — 28
of 32 — of strains of metastatic prostate cancer he has studied.
“Genetic inhibition of CDK5 activity blocked cell motility,
invasion, and, in ananimal model, reduced metastases by 79 percent,”
he continues, “suggesting CDK5 as a potential therapeutic
target to limit metastasis in prostate cancer.
”There’s good news already in this story —some CDK5-blocking
drugs already exist, for treatment of neurodegenerative disease. This
means that Nelkin and colleagues have hit the ground running, and are
testing these drugs in laboratory animals with metastatic prostate cancer.
They are also looking to develop laboratory tests to monitor CDK5
activity in prostate cancer cells.
What this means for bone:
“Bone is the most significant metastatic site for prostate cancer,”
notes Nelkin. “Blocking CDK5, in addition to inhibiting
metastasis, may also inhibit the ability of prostate cancer to survive
and grow in bone.” Nelkin and colleagues will be exploring this,
using an animal model of prostate cancer metastasis in bone. They will
also see whether blocking CDK5 makes other chemotherapeutic drugs
more effective. “We envision that this could provide a therapeutic
benefit, especially for patients with limited disease,” he says.
For example, blocking CDK5 in a man with prostate cancer that
has spread only to the lymph nodes, “could prevent further progression
— potentially allowing effective therapy or even cure by other forms
of treatment. We speculate that clinical trials could begin within one
to two years ofthe successful completion of this project.”