Tackling Prostate Cancer From All Angles
When it comes to combating prostate cancer, the most common cancer in men, Joshua Lang, MD, MS, thinks the best approach comes from many angles. Not only is Lang a medical oncologist at the UW Carbone Cancer Center, with a practice focusing primarily on prostate cancer, but he also runs a research laboratory built around developing new cancer treatments and conducts clinical trials to test new drugs.
“Our goal is to look at the full spectrum. We see what our patients are facing in the clinic and then use that information to come up with new therapeutic options,” Lang said.
This approach led to a new clinical trial for a prostate cancer treatment that Lang hopes to begin this year. The trial will be for an experimental drug that has, until this point, mainly been studied in clinical trials for women with triple-negative breast cancer. The drug, called IMMU-132, targets the protein TROP-2 that is found in some breast cancers. Lang and his colleagues wanted to determine if this drug could be useful for men with prostate cancer.
First, the researchers took small blood draws from consented patients with advanced prostate cancer, and asked if they could detect cancer cells that contained TROP-2.
“Turns out we could, and as we tested more and more of these patient samples, we found it was pretty frequently expressed,” Lang said. “In the trial we’re proposing, we’d like to test if IMMU-132 offers a clinical benefit to men with prostate cancers that contain the TROP-2 target.”
Lang emphasized the benefits of working with samples from patients to discover new treatment options such as this one.
“We give all these treatments to patients that attack their cancer, but don’t completely eradicate it. That selective pressure changes the disease in ways we really don’t understand,” Lang said. “Working with patient samples lets us get a better understanding of how the cancer can change from a treatment and become resistant. With that information, we can try to devise ways to target that resistance.”
Many prostate cancer patients provide blood samples not as part of their standard treatment, but to benefit cancer research at UW Carbone.
“We have these amazing patients at the Cancer Center who donate blood samples just for research,” Lang said. “It’s truly an honor to work with these samples, since they come from patients who don’t expect the research to benefit them, but will hopefully help someone else later.”
Working with the patient blood samples, however, can be tricky, since the blood cells vastly outnumber the cancer cells.
“There’s about one tumor cell per billion blood cells, so the current technologies weren’t suitable to isolate only the tumor cells,” Lang said.
He started collaborating with UW Carbone biomedical engineering professor David Beebe, Ph.D., to create a device to suit their needs.
“We developed a new microscale ‘chip’ that allows us to better handle and evaluate these rare cancer cells,” Lang said. “We can capture them, do protein analysis, and extract RNA or DNA to study how the cancer is changing at the molecular level.”
These devices, for example, allowed Lang to identify the TROP-2 protein in prostate cancer cells. But they will also allow him to study other factors that regulate cancer development and progression. One area Lang has recently become interested in is known as epigenetics. Epigenetics looks at how changes in gene levels in cells makes them cancerous, even if there is no detectable mutation in that gene.
“Epigenetics is a field we really don’t understand well,” Lang said. “But, prostate cancer cells potentially take advantage of epigenetic mechanisms to hide from the immune system more effectively or to become more aggressive, invasive, and treatment resistant.”
Lang and Beebe are currently developing new technologies to aid in epigenetics research. The focus of this epigenetic research is on advanced prostate cancer, but they hope that as they understand more about epigenetics, these tools could be applied to other diseases as well.
Date Published: 01/11/2018