A team of Purdue University researchers has synthesized a molecule that finds and penetrates prostate cancer cells and has created imaging agents and therapeutic drugs that can link to the molecule and be carried with it as cargo.
A radioimaging application used for body scans is expected to enter clinical trials this fall, and an optical imaging application used to measure prostate cancer cells in blood samples is already in clinical trials.
Philip Low, the Ralph C. Corley Distinguished Professor of Biochemistry who led the team, says a targeted treatment could be much more effective in treating cancer and would greatly reduce the harmful side effects associated with current treatments.
"Currently none of the drugs available to treat prostate cancer are targeted, which means they go everywhere in the body as opposed to only the tumor, and so are quite toxic for the patient," says Low, who is a member of the Purdue Cancer Center. "By being able to target only the cancer cells, we could eliminate toxic side effects of treatments. In addition, the ability to target only the cancer cells can greatly improve imaging of the cancer to diagnose the disease, determine if it has spread or is responding to treatment."
The molecule Low's team created attaches to prostate-specific membrane antigen, or PSMA, a protein that is found on the membrane of more than 90 percent of all prostate cancers. It also is found on the blood vessels of most solid tumors and could provide a way to cut off the tumor blood supply, Low said.
"A lot of new drugs are being designed to destroy the vasculature of solid tumors, and, if they could be linked to this new targeting molecule, we could have a two-pronged attack for prostate cancer," he says. "We could not only kill the prostate cancer cells directly, we could also destroy the vasculature that feeds the tumors."
There also is potential for the targeting molecule to be used to attack the vasculature of solid tumors of other types of cancers, Low said.
Two papers detailing the work of the Purdue team were published in Molecular Pharmaceutics. Endocyte Inc. funded the work.
The team's animal study data shows an ability to eliminate human prostate cancer cells in mice with no evidence of collateral toxicity in normal tissue.
"The molecule acts like a homing device for prostate cancer," says Sumith Kularatne, a graduate student in Purdue's chemistry department and first author of both papers. "PSMA, which is found only on prostate cancer cells and tumor blood vessels, acts as the homing signal that the molecule targets. The molecule and its cargo go only to cancerous tissue, leaving healthy tissue unharmed."
Once the molecule reaches the PSMA protein, it binds to it. The molecule is designed with a specific shape that fits with the protein like a key to a lock, Kularatne said. The molecule and its cargo are then carried inside the cell with the protein as it goes through its normal cycle.
In 1995 Low developed a similar method to infiltrate cancer cells by attaching treatments to the vitamin folate, which many cancers rapidly consume. This method provided a "Trojan Horse" entry of large treatment molecules that otherwise would not be able to enter cancer cells.
Low was inspired to find a similar way to target prostate cancer, which does not have the same appetite for folate, he says.
A clinical trial of the radioimaging application is expected to begin at the Indiana University Medical Center in the fall through a collaboration between the Purdue Cancer Center and the Indiana University Cancer Center with additional support from Endocyte Inc.
There is currently only one radioimaging agent for prostate cancer approved by the Food and Drug Administration.
Already in clinical trials is an optical imaging application that involves attaching a fluorescent dye to the targeting molecule and mixing it with a patient's blood sample.
Circulating prostate cancer cells in the sample fluoresce and are easily measured to help in diagnosing patients with prostate cancer. Researchers also are investigating whether this could be used to evaluate a patient's response to therapy, Low says.
Source: Purdue University