The Melanoma Age of Enlightenment
Pictured above: Dermatology professor Nihal Ahmad, PhD, and his research group look at the biology of melanoma and are identifying more features that can be targeted specifically with drugs.
Melanoma medical oncologist Mark Albertini, MD, thinks we are in a “true age of enlightenment” when it comes to treating the skin cancer, especially with immunotherapy-based treatments.
“I’ve been doing this about a quarter of a century, so unfortunately I’ve lived through the dark ages where we had painfully few treatments for advanced melanoma,” Albertini said. “And then, with the advent of primarily laboratory-based understandings of targeted therapies such as the successful B-raf inhibitors, and perhaps more importantly with identifying ways to unleash immune cell attacks against the cancer, we’re now seeing responses in up to 50 percent of patients.”
Not content to stop at 50 percent, Albertini and other melanoma researchers at the UW Carbone Cancer Center are studying ways to improve response and survival rates even more.
Albertini’s research group takes the immunotherapy approach to studying melanoma. Immunotherapies have been incredibly successful in some patients, but other patients have shown no response. His group has already developed a way to take blood and biopsy samples from patients with advanced-stage melanoma and to isolate immune cells that were activated by the patient’s natural immune response to the cancer.
Now, in work funded by a UW Carbone pilot grant and melanoma philanthropy group Ann’s Hope, Albertini is taking these activated immune cells and using them to look for markers that will help him and other clinicians predict who is going to respond to immunotherapy. He is working in collaboration with UW Carbone medical imaging researchers Robert Jeraj, PhD, and Steve Cho, MD.
“We have a four-patient pilot study ongoing now where these patients are getting the standard-of-care treatment but they’re generously allowing additional biopsy and imaging studies to take place,” Albertini said. “These studies have no direct benefit for these individual patients, but they will go a long way in helping us figure out what’s working and what’s not in the treatments, and if there are any signatures we can identify to tell who in fact is going to go on to get a good response or not.”
Dermatology professor Nihal Ahmad, PhD, and his research group look at the biology of melanoma and are identifying more features that can be targeted specifically with drugs. Previously, his lab showed that a pro-cancer protein, PLK-1, was present in higher levels in cancerous melanomas compared to the non-cancerous melanocyte skin cells. In both cell culture and mouse models, they showed found that reducing PLK-1 levels led to death of the cancerous, but not non-cancerous, cells. Perhaps most promising, the PLK-1-targeting drug is already in clinical trials for other cancers.
“Melanoma, like any cancer, is a disease where a number of protein pathways are affected, so when a clinician wants to treat melanoma, he or she will typically go with a multiple drugs,” Ahmad said. “But we faced a significant problem of resistance. That’s why it’s important to hit melanoma with multiple drugs, and to find new targets such as PLK-1 for when drug resistance develops.”
Much of Albertini and Ahmad’s previous lab research has informed the development of melanoma clinical trials at UW Carbone and elsewhere. They still direct their current research with the same goal of being translated to the clinic, increasing survival rates and decreasing the need for non-specific – and less effective – chemotherapies.
“We used to use chemotherapy a fair amount to treat melanoma without very positive outcomes,” Albertini said. “But now, with these laboratory-based understandings, survival rates are increasing and it’s been a while since I’ve written a chemotherapy prescription for melanoma.”
Date Published: 08/16/2018