Breakthrough treatments offer hope for melanoma patients

Melanoma is one of the cancers with declining a mortality rate in the United States, according to the American Cancer Society’s annual report released in January 2025. The annual report on cancer trends found that the five-year survival rate for distant-stage melanoma had doubled from 18% for patients diagnosed in 2009 to 35% in the 2014-2020.

Researchers estimate that just over 2 million new cases of cancer will be diagnosed in 2025. Invasive melanoma will account for approximately 100,000 of those, or roughly 5%. The American Cancer Society researchers projected that there will be 618,120 cancer deaths in the U.S. in 2025, with melanoma accounting for 8,430 of them, or approximately 1.3%.

The immunotherapies used to treat melanoma now include well-established drugs such as Keytruda (pembrolizumab) and Opdivo (nivolumab) and newer ones such as Amtagvi (lifileucel), which uses T cells extracted from the melanoma tumor and amplifies them so they attack the tumor more effectively.

But skin cancer rates among seniors are projected to skyrocket over the next 25 years, with some forms expected to increase by more than 140%, according to a report published in May 2025 in JAMA Dermatology.

The research analyzed data from more than 200 countries between 1990 and 2021 and found that adults 65 years or older experienced more than 150,000 melanoma cases, approximately 1.5 million squamous cell carcinoma cases, and 2.8 million basal cell carcinoma cases in 2021 alone. The researchers estimate that these rates will jump in some cases by nearly threefold as the aging population grows.

The study projects melanoma prevalence will decline by up to 46% by 2050, but basal cell carcinoma incidence could more than double, with a 44% increase in disability-adjusted life-years, a measure combining years of life lost and years lived with disability.

Melanoma is among the most aggressive forms of skin cancer, and while the introduction of immune checkpoint inhibitors over the past decade has significantly improved outcomes, many patients eventually stop responding.

New research has shed some light on why that might be. UCLA researchers have found that DNA changes can help tumor cells sidestep self-destruct signals sent by the immune system. Melanoma tumors develop large-scale changes in their DNA that systematically disable the cellular machinery for self-destruction. These genetic alterations work like a defense system, erasing multiple genes that would normally cause cancer cells to die when targeted by immune cells while making extra copies of genes that prevent cell death. This study was published in Immunity in November.

Additionally, over the last year, exciting new research has begun to offer hope for patients with melanoma. A promising therapy in development is a next-generation oncolytic virus — a genetically engineered herpes simplex virus type 1 (HSV-1) — that was able to shrink advanced melanoma tumors. This research was presented at the 2025 American Society of Clinical Oncology annual meeting in July.

RPI (vusolimogene oderparepvec) contains a strain of herpes simplex virus engineered with a protein that assists with fusion (GALV-GP-R-) and granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine intended to maximize tumor-killing potency. Researchers found that not only did the injected tumor size shrink in one-third of the patients by 30%, but also that patients’ uninjected tumors also shrank or even disappeared. In the trial, the objective response rate was 32.9%.

A global phase 3 trial is ongoing, and Replimune has resubmitted its biologics license application to the FDA. The agency has assigned a review date of April 10, 2026.

Early research for melanoma

This year also saw exciting developments earlier in the development pipeline. An exciting treatment possibility is a therapy that involves fecal microbiota transplants using healthy donor stool. In a small phase 1 study, patients receiving the transplant along with standard immunotherapy survived more than four years. Researchers John Gordon Lenehan, M.D., and Saman Maleki Vareki, Ph.D., both of Western University, followed 20 patients with stage III or IV melanoma who received a single oral fecal transplant followed by either Opdivo (nivolumab) or Keytruda (pembrolizumab). The median overall survival was 53 months, and the median progression-free survival was 30 months.

“The gut microbiome influences the response to [immune checkpoint inhibitors], and microbiome manipulation with oral [fecal microbiota transplantation] capsules in this small cohort was safe and appeared to improve clinical outcomes and possibly avoid primary resistance,” the study authors wrote in a paper published in the Journal for ImmunoTherapy of Cancer.

Another study is under way to characterize the actual benefit of this combination therapy, researchers said.

Another potential therapy is an engineered CD40 antibody, 2141-V11, that can bind to a specific immune receptor and, when directly injected into tumors, can trigger a systemic immune response. In a phase 1 trial, 6 of the 12 patients with advanced cancers that had spread to the skin, including melanoma, breast cancer and kidney cancer, saw their tumors shrink, including two patients who achieved complete responses that lasted more than a year.

“Seeing these significant shrinkages and even complete remission in such a small subset of patients is quite remarkable,” first author Juan Osorio, M.D., said in a news release. Osorio is a medical oncologist at Memorial Sloan Kettering Cancer Center. The research was published in Cancer Cell in October.

Several ongoing studies are now testing 2141-V11 in either phase 1 or phase 2 trials in specific cancer types, including bladder cancer, brain tumors, and prostate cancer.

A development in cancer detection is a wearable patch that one day could be used to determine whether moles or other lesions on the skin are cancerous. The patch measures distinct electrical patterns, which indicates how easily electrical signals pass through living tissue. Cancerous areas have different electrical properties than healthy skin because malignant tumors affect cell shape, density, and blood flow. The device can detect these differences, providing information beyond what visual inspection typically provides.

The patch works without batteries or computer chips and uses magnetic signals from a separate reader device to measure how easily electrical currents pass through skin tissue. It was developed by Mohammad J. Moghimi, Ph.D., assistant professor of biomedical engineering at Wake Forest University School of Medicine.