How Do You Measure a “Smart Bomb?”

isaac prostate cancer discovery
John Isaacs
Years ago, John Isaacs, Ph.D., and Samuel Denmeade, M.D. chose as their academic mission undoubtedly the most difficult area of prostate cancer — the one with the greatest need — metastasis. When cancer spreads beyond the prostate, it is difficult to cure, and when it sows its seeds at far-flung sites in the body, it is impossible to cure. Cancer can be delayed, often for years, but it cannot be killed.

The beauty of this approach is that it does not affect healthy tissue, and in laboratory studies using human prostate tumor cells, these “smart bombs” are indeed shrinking the cancer.

One reason is that it’s impossible to know exactly where the cancer is. So Isaacs, professor of urology, and Denmeade, associate professor of oncology, have been making “smart bombs” that — like heat-seeking missiles— follow a trail. In this case, the missiles are designed to track PSA, which, normally, is an enzyme that, as the old commercials used to say, “slices and dices” — except what it cuts are pieces of protein, and this only within cancerous tissue. Once the molecular missile finds its target, it attacks the prostate cancer cells by restarting a normal process that cancerous cells lack — the ability to die; it makes them mortal again. The scientists have identified several new “smart bomb” drugs that cause the cells to kill themselves; this process, which happens all the time in normal cells, is known as apoptosis.

The beauty of this approach is that it does not affect healthy tissue, and in laboratory studies using human prostate tumor cells, Isaacs and Denmeade have found, these “smart bombs” are indeed shrinking the cancer. How well are they working? That’s the next question, and the scientists have designed and synthesized some specially tagged molecules — which can be seen through radiologic imaging — to act as little signal flares, to show where the cancer is, and if all goes well, to show that it is being killed.

“These molecules are activated by being cut up, either by PSA (prostate-specific antigen) or by another enzyme on the prostate cell’s surface, PSMA (prostate-specific membrane antigen),” says Isaacs. “Since both of these enzymes are only expressed in high levels by prostate cells, they will only be activated at the metastatic sites where the prostate cancer cells are growing. This way, we can see how well the individual sites of metastasis will respond, and know how well our drugs are working.”


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