How Melanoma Becomes Resistant to Treatment

Melanoma cell mechanisms that promote resistance to treatment identified.

The skin cancer known as melanoma can become resistant to treatment, but new research is beginning to unravel the secrets of tumor resistance.

Researchers at the University of California Los Angeles have identified specific genes in advanced melanoma tumors that can make them resistant to treatment.

Although melanoma treatment has become more advanced and in many cases is successful, tumors can reappear in some patients after treatment. The cancer is currently treated with anti-PD-1 antibody pembrolizumab, known by the brand name Keytruda, that is a form of immunotherapy.

“The tremendous promise of immunotherapy is to engage our body’s immune defenses to fight cancer, but the results must be long-lasting,” study co-leader Antoni Ribas, MD, said in a press release. “We have now identified for the first time mechanisms that cancer cells can use to avoid recognition by the immune system’s T cells and decrease sensitivity to their attack.”

Dr. Ribas is the director of the UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program.

Dr. Ribas and research co-leader Jesse Zaretsky, the study’s first author and a doctoral student in Ribas’ lab, began their research by analyzing biopsies of melanoma tumors from patients who had been treated with pembrolizumab. They compared biopsies taken before treatment and after patients had relapsed which could occur several months to years after treatment.

The researchers found disruptions in the tumors’ genetic patterns. The genes involved included one called B2M and two others, JAK1 and JAK2.

The loss of the first gene changed how the tumor was recognized by the immune system. In the remaining genes, disrupted function limited the effectiveness of the immune system, which was no longer able to kill the cancer cells.

“These findings can help open up a whole new potential area of research and allow us to better understand acquired resistance to these promising treatments,” Zaretsky said in the press release.

The scientists hope to find new treatment methods or ways to make current treatment more effective as they continue their research.

The study was published in the June issue of the New England Journal of Medicine.

Partial funding for the study was provided by the National Institutes of Health.

None of the researchers reported a relevant conflict of interest.

University of California, “Study sheds light on how advanced melanoma resists treatment”
New England Journal of Medicine, “Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma”

Written by: Beth Greenwood, RN | Medically reviewed by: Dr. Robert Carlson, M.D.