Like a medical marathon, physicians run to keep up with metastatic cancer as it races ahead, outsmarting one treatment after another, and this is especially true for patients with metastatic melanoma.
Currently, there is no reliable blood test to detect or monitor this extremely lethal disease, which has a dismal 5-year survival rate of only 20 percent, meaning only one in every five patients remains alive 5 years after diagnosis.
Now, some of the nation’s top biomedical institutes — led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope — have received a $2 million federal grant towards discovering a new way to detect and track metastatic melanoma and understand how it escapes treatment.
“To monitor melanoma during treatment, the only available test today is imaging, such as a CT scan,” said Dr. Muhammed Murtaza, Co-Director of TGen’s Center for Noninvasive Diagnostics and the study’s principal investigator. “But you can’t scan patients very often during treatment because it’s expensive and exposes patients to radiation. If we can develop a blood test to monitor treatment response, we may be able to use it weekly.”
Dr. Murtaza proposes to isolate strands of DNA, known as circulating tumor DNA (ctDNA), which are shed from tumors and circulate in the bloodstream. He would use simple blood samples to capture ctDNA, and use these strands to measure changes in metastatic melanoma. Analyzing serial blood samples weekly or monthly would allow physicians to effectively monitor the patient’s progress during therapy.
In preliminary studies, this technique has already shown promise in detecting and monitoring different types of cancers, but studies with melanoma have only been conducted on a few patients. The challenge is to understand at what point during treatment, and by how much, do ctDNA levels change, and whether these changes can predict if a patient will do well on therapy. To do so, this study envisions analyzing ctDNA levels during treatment in more than 100 patients with melanoma.
Melanoma is the deadliest form of skin cancer, and is often found on the chest, back and legs. But different types of melanoma can originate in different parts of the body, and metastatic melanoma often spreads to the lungs, lymph nodes, liver, bones and brain.
Current therapies work for a time on metastatic melanoma, but their benefits are temporary, and this rapidly mutating cancer eventually slips free and continues to spread out of control, requiring new types of therapeutics.
“Cell-free DNA has many advantages in being precise, individualized, sensitive, and quantifiable. We think we can save patients time, reduce their exposure to scans, and decrease overall expense while providing important information about tumor evolution to the treating oncologist,” said one of the project collaborators, Dr. Alan Bryce, a physician-scientist at Mayo Clinic’s Arizona campus, whose specialties include melanoma.
This five-year, $2 million R01 grant was issued by the National Institutes of Health (NIH). Also contributing to this study are Dr. Patricia LoRusso at Yale Cancer Center, and Dr. Antoni Ribas at the University of California at Los Angeles (UCLA).
“I’m very excited to be included in this research grant,” said Dr. LoRusso, D.O., Associate Director of Experimental Therapeutics at Yale Cancer Center. “Despite significant advancements in therapies for metastatic melanoma over the past few years, it continues to be a life threatening illness for many patients.”
This project builds on the work of Dr. Murtaza and Dr. Ribas through their Stand Up To Cancer (SU2C) Phillip A. Sharp Innovation in Collaboration Award. It also builds on the work of Dr. LoRusso and Dr. Jeffrey Trent, TGen President and Research Director — in collaboration with Mayo Clinic’s Arizona campus — through their SU2C Melanoma Research Alliance Melanoma Dream Team.