Understanding the Physics of Prostate Cancer

One of the fundamental mysteries of advanced prostate cancer is, why does it become resistant to hormonal therapy, and even to chemotherapy? Something happens to aggressive cancer; it learns to evolve quickly, to become a moving, hard-to-kill target. “When this happens,” says Robert H. Getzenberg, Ph.D., the Brady’s Research Director, “another anti-androgen or chemotherapy drug is not going to be the answer. Instead, we need to attack the mechanism through which cancer cells develop resistance, and increase their sensitivity to currently available agents.” Brady scientists are doing this, in two major initiatives:

Physical Sciences in Oncology Center:
In a multidisciplinary effort, working together with physicists and engineers from Princeton University, cancer biologists from the University of California – San Francisco, scientists from the Scripps Institute and the University of California-Santa Barbara, Getzenberg, along with Brady colleagues Robert Veltri, Robert Ikvov and Donald Coffey, has received a grant from the National Cancer Institute to support a Physical Sciences in Oncology Center.

“ This is the ‘anti-silo’ approach,
bringing basic scientists from the
non-medical research world to
the study of prostate cancer.”

“This is an excellent example of one of the strengths of the Brady,” says Getzenberg, the Donald S. Coffey Professor of Urology. “Scientists are often accused of working in their own little silos, and not collaborating with others. This is the ‘anti-silo’ approach, bringing basic scientists from the nonmedical research world to the study of prostate cancer.” Together, these scientists are concentrating on the nucleus, the “brain” of the cell, to understand the evolutionary ability of cancer cells. “Rearrangements in the DNA , along with changes in the shape and texture of the nucleus, are hallmarks of cells that develop resistance,” says Getzenberg. “Our goal is to understand this element of the process.”

Thermal-enhanced Metastatic Therapy (TEMT):
This is another interdisciplinary, multicenter project aimed at making aggressive prostate cancer easier to kill. Supported by Safeway/PCF, through money raised with many individual donations at the cash register, this program combines physics, chemistry, electrical engineering, material science and engineering, nanotechnology, cancer biology, and radiation oncology. The basic idea here, inspired by questions asked years ago by Donald S. Coffey, Ph.D., is that cancer cells become easier to kill when they are gently heated;

How do you make aggressive,
micrometastic cancer cells easier
to kill? Target them with tiny iron
particles, then gently heat them up.

even a few degrees higher than the regular body temperature is enough to make them vulnerable. Using tiny iron-containing particles that are heated with an alternating magnetic field, the Hopkins team is targeting cells that have metastasized, making them more sensitive to radiation and chemotherapy. This year, the team, including Coffey, Getzenberg, Theodore DeWeese, Robert Ivkov, Shawn Lupold and Prakash Kulkarni, has synthesized these nanoparticles and chemically modified them. The goal is to hit only the cancer cells, and not the nearby healthy tissue; thus, the scientists are working on ‘tagging’ the nanoparticles with a chemical substance that will target them to the desired cells. The team has also designed and built a device that generates powerful fields, causing these particles to heat up, allowing for longer exposure of normal tissue to highintensity radiation fields that only affect the nanoparticles. “Our tests with animal models were successful,” says Getzenberg, “and we are now working with electrical engineers at Hopkins to test designs that will be used in the clinic. If we are successful, this novel therapeutic approach would allow clinicians to trace micrometastatic tumors, and selectively target them to enhance their sensitivity to therapy.” Also working on the TEMT project are scientists Ken Pienta, at the University of Michigan, and Martin Gleave, at the University of British Columbia, Canada.

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