Spot On: Sylvester Comprehensive Cancer Center’s Novel Discoveries and Treatments Advance Melanoma Care
Summary
- Doctors and researchers at Sylvester Comprehensive Cancer Center are making encouraging inroads in the treatment of melanoma.
- Dr. Barbara Bedogni developed a neutralizing antibody that shows promise for improving immunotherapy response to melanoma treatment.
- Dr. Jose Lutzky is leading a team of doctors running some 15 clinical trials and treating about 550 melanoma patients annually.
Doctors and researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, are making encouraging inroads in the treatment of melanoma, the deadliest form of skin cancer. As the nation pays homage to Melanoma Awareness Month in May, the pioneering work at Sylvester is bringing hope to patients at a time when melanoma cases are on the rise, with the American Cancer Society estimating 104,960 new cases of melanoma and 8,430 deaths this year alone.
In the lab, Sylvester researcher Barbara Bedogni, Ph.D., associate professor in the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, and her team developed a novel, neutralizing antibody that shows promise for improving immunotherapy response to melanoma treatment.
Meanwhile, in the clinic, melanoma expert Jose Lutzky, M.D., director of Cutaneous Oncology Services and Cutaneous and Ocular Oncology Site Disease Group lead at Sylvester, is leading a team of doctors running some 15 clinical trials and treating about 550 patients annually.
“We are one of the most active centers in the country in the treatment of melanoma, having options for patients at all stages of the disease and particularly for uveal melanoma,” he said.
Melanoma Breakthroughs in the Lab
After Dr. Bedogni and her team discovered the role of Notch1, a protein highly expressed in melanoma that is associated with lower response of patients on immunotherapy, they worked on developing a neutralizing antibody to improve immunotherapy in a way that is not toxic. They published their findings in a recent paper in the Journal of Experimental & Clinical Cancer Research.
“We are still working on it, but by blocking Notch1, we can cause DNA damage so, when the cells are hit with radiation, they are much more sensitized to treatment for melanoma brain metastasis,” said Dr. Bedogni, who works closely with Sylvester associate scientist Varsha Thakur, Ph.D.
Dr. Bedogni’s lab also is nailing down new diagnostic pathways, collaborating with Brian Morrison, M.D., associate professor in the Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery and an expert on nail melanoma. They’re looking for a way to use nail clippings instead of biopsies to diagnose this rare form of the disease.
“A dark stripe on the nail could be melanoma, but it could just be a bruise,” Dr. Bedogni said. “Right now, the only way to identify melanoma is to do a biopsy that is very invasive.”
If the team can successfully extract high-quality RNA from a nail clipping, which is complicated because RNA is delicate, Dr. Bedogni can then compare RNA and DNA sequencing from the clippings to the gene signatures on biopsies. That will allow her to identify genes for testing and determine if a lesion is high risk.
Advancements in the Treatment of Melanoma
The use of immunotherapy revolutionized the treatment of melanoma 15 years ago, allowing half of the patients with advanced melanoma to live at least a decade past diagnosis. The other 50% of patients, the ones who don’t respond or relapse despite checkpoint inhibitors, are the target of current research, Dr. Lutzky said. A more recent breakthrough came last year with the FDA approval for the first cellular therapy for metastatic melanoma. Known as tumor-infiltrating lymphocyte therapy (TIL), it uses a patient’s own immune cells to target the cancer.
At Sylvester, patients participate in clinical trials or are treated with other forms of therapy, with ongoing cell therapy trials for advanced disease, Dr. Lutzky said. In one trial, T cells from a patient’s peripheral blood are molecularly and genetically altered to target specific antigens in the tumor. In another, oncolytic virus immunotherapy selectively infects and kills cancer cells while sparing healthy cells and generating an immune response.
When it comes to uveal melanoma, a rare form of melanoma that begins with cancer in the eye and tends to spread to the liver, Sylvester and Bascom Palmer Eye Institute have teamed up on numerous clinical trials. One that just launched targets those at high risk for recurrence with a drug investigated at Bascom Palmer that, in preclinical studies, prevents or slows tumor cell growth in uveal melanoma.
Prevention, the Best Medicine
Sun exposure is the greatest risk factor for melanoma, so the Sunshine State carries a high caseload. While those with atypical moles should be monitored regularly by a dermatologist, the primary risk for developing melanoma is sun exposure, especially during childhood and young adulthood.
“You want to minimize sun exposure, especially between 10 a.m. and 4 p.m., because that is when there is the highest amount of UV radiation,” Dr. Lutzky said. “You want a sunscreen with an SPF of at least 30, and you want to reapply every two hours. You don’t have to live in a cave, but you have to be sun smart.”
Tags: cancer research, Dr. Barbara Bedogni, Dr. Jose Lutzky, immunotherapy, melanoma, skin cancer, Sylvester Comprehensive Cancer Center