The merging of two discoveries provides a novel way to deliver cell destruction to prostate cancer. At the center of the research are two things familiar only to scientists—aptamers and siRNA.

Aptamers are small molecules that work much like antibodies to target things—like cancer—that don’t belong in our bodies. They are really good at binding to other molecules. Prostate cancer expert Shawn Lupold, Ph.D., developed an aptamer that targets the prostate-specific membrane antigen (PSMA), a protein found in most prostate cancer cells.

Today, the process is automated, and Lupold can make his aptamer in two weeks, but when he first took on the project as a graduate student, it took him five years to drill down to just the right chemical formulation among many billions of molecules.

At the same time Lupold was working on his aptamer, Theodore DeWeese, M.D., Director of Radiation Oncology and Molecular Radiation Sciences was working on another technology called small in terfering RNAs (siRNA), that have the ability to turn off genes. Radiation therapy kills cells cancer by damaging their DNA. Some cancer cells, however, are able to repair the damage and survive, so DeWeese’s plan was to use siRNA to turn off genes that help perform these repairs. Lupold’s aptamer would allow him to do it selectively—causing harm only to cancer cells.

Lupold’s prostate cancer-targeted aptamer was the perfect delivery vehicle for DeWeese’s radiation-sensitizing siRNAs. Their final product was an aptamer that used PSMA as a chemical GPS system to guide the siRNA to prostate cancer cells where they block DNA repair mechanisms, making prostate cancer cells ultra sensitive to radiation therapy.

“It’s almost as if we turned up the radiation, but we did it molecularly,” says Lupold. Actually increasing the dose of radiation therapy would surely kill more cancer cells but be far too toxic to normal cells. This approach has the same effect and is safe.

Their treatment worked well in animal models, and aptamers are already FDA-approved for other medical purposes, so Lupold and DeWeese do not anticipate any safety problems. To move the therapy to clinical trials, they will need about $1 million to outsource the production of clinical-grade aptamers. 

Lupold and DeWeese are also exploring aptamers as a way to safely deliver and track radiation-releasing alpha particles to painful and deadly prostate cancer cells that spread to the bone. 

DeWeese says the cancer-targeting siRNA aptamers are unique to Johns Hopkins and considered the gold standard. The current version is specifically targeted to prostate cancer, but he says with an adjustment to the chemical GPS, they can be adapted to target essentially any cancer.