Melanoma is the deadliest type of skin cancer despite accounting for only a small percentage of all skin cancer diagnoses. Existing therapies can be effective, but in many cases advanced melanomas develop resistance to treatment.
Researchers at Emory University have synthesized a novel molecule that could pave the way for future advancements in melanoma treatment. The molecule, named indolium 1, has demonstrated ability to block the growth of melanoma cells and is well-tolerated in animal subjects, according to findings published in the journal Antioxidants.
“Only about 15 to 20% of melanomas respond to immunotherapy and targeted therapy, so there is an unmet need for new treatments,” says senior author Jack Arbiser, MD, PhD. “This novel compound works differently than any other therapies on the market and shows promise as a potential treatment for melanomas with poor prognostic features.”
Most melanomas are caused by a mutation in the BRAF molecule that can stimulate cells to grow out of control. Targeted therapies aim to inhibit molecules in the BRAF pathway that regulate cell growth, and immunotherapies help the body mount a stronger response against cancer cells.
While these treatments can shrink and slow the progression of melanomas, cancer cells that have developed resistance to therapies are often left behind. In developing indolium 1, Arbiser and colleagues sought to target alternative pathways that have not yet been the subject of significant study to combat the aggressive cancer cells that remain.
Indolium 1 is a compound in the class of triphenylmethanes, which previous studies have shown to inhibit the enzyme that drives melanoma growth. The new findings have demonstrated a novel mechanism of action in indolium 1 which induces a tumor-suppressing gene, suggesting that additional research in humans is warranted.
“Further study of this compound is necessary before it can benefit individuals with advanced melanoma,” Arbiser says. “Our findings suggest that indolium 1, administered in sequence with existing therapies, could have significant implications for cancer patients.”
Arbiser began practicing as a dermatologist at Emory Healthcare in 1998. He is Thomas J. Lawley Professor of Dermatology at Emory University School of Medicine and a member of the Discovery and Developmental Therapeutics research program at Winship Cancer Institute. Rakan Radi, MD, and Christina Huang of the Department of Dermatology and Justin Elsey and Victor G. Corces, PhD, of the Department of Human Genetics co-authored the study.