After finishing treatment, cancer patients live with the nagging anxiety that their cancer will return. Today, physicians have few ways to assure patients about their future. That is why researchers such as City of Hope’s Beth Singer, Ph.D., and Steve Smith, Ph.D., seek better methods to predict cancer recurrence.
Singer and Smith, in collaboration with Laura Crocitto, M.D., assistant professor of surgery, Timothy Wilson, Pauline and Martin Collins Family Chair in Urology, and Lawrence Weiss, M.D., chair of the Department of Pathology, are looking for such an answer for men with prostate cancer — by using nanotechnology.
|From left, Steven Smith, Beth Singer and Laura Crocitto discuss the use of nanotechnology for prostate cancer patients. (Photo by Darrin S. Joy)|
Smith, professor in the Division of Urology and Urologic Oncology, and Singer, a postdoctoral fellow in Smith’s lab, have spent several years building nanoparticles aimed at detecting prostate cancer. In the course of their work, they have found evidence that the nanoparticles might be able to tell the difference between aggressive cancer cells that are likely to come back after treatment and those that are less likely to recur.
Singer and Smith hope to be able to use the nanoparticles to look for aggressive tumor cells in patients’ prostate biopsy samples.
About 10,000 times smaller than the diameter of a human hair, their nanoparticles consist of a “Y”-shaped piece of DNA with a specially designed fusion protein attached to each of the three arms. “It winds up being a rather large molecule, which of course makes it really small,” quipped Smith, who serves as principal investigator on the study.
The fusion protein is actually two proteins combined: One is an enzyme that connects to an arm of the DNA, and the other, called thioredoxin, recognizes molecules that are common in many cancer cells.
“Previous research has shown that thioredoxin may play an important role in the development of cancer,” said Singer. So, Smith and Singer reasoned that using thioredoxin in the fusion protein would give the nanoparticle the ability to detect cancer cells.
The nanoparticle also contains a fluorescent dye that glows under ultraviolet light. That can signal when the nanoparticle has found a tumor cell: A glowing cell would be cancerous, while dark cells would be normal.
Singer and Smith exposed different types of normal and tumor cells to the nanoparticles and measured the amount of fluorescent glow. As expected, the normal cells glowed little if at all, while cancer cells glowed more brightly.
In a surprising result, though, some cancer cells glowed more than others. The scientists believe the amount of fluorescence might indicate how aggressive the cancer is and whether or not the cancer is likely to return.
“What we want to do now is use the nanoparticle in patient samples and compare that with current standard methods” of measuring risk of recurrence, said Smith. “The method is very sensitive and should be faster than those we use now.” It also might be less expensive, he added.
The team recently received a $166,000 grant from the National Cancer Institute to advance the method.
Alex Lee, a student in the Eugene and Ruth Roberts Summer Student Academy, also contributed to the project.