“Metastatic cancer” refers to a cancer that began in one location in the body but spread to one or more other locations. Metastatic melanoma is a type of skin cancer that has spread beyond its initial location in the skin. Common sites of metastasis are other areas of the skin, deeper layers of the skin, lymph nodes, the lungs, the liver, bones, and the brain.
The initial treatment of metastatic melanoma can involve a number of different therapies. Localized tumors can be treated with surgery, radiation therapy, and cancer vaccines that are injected directly into a tumor.
Treatment for metastatic melanoma typically involves targeted therapies and/or immunotherapy, especially when cancer is widespread. These are systemic therapies, cancer drugs that travel through the bloodstream to reach cancer cells throughout the body.
The type of therapy and combination of therapies recommended will vary from one person to another. The location of the tumors, the stage of the cancer, and a person’s age, overall health, and tolerance for side effects all need to be considered.
Treatment recommendations may also need to be revised depending on how the cancer responds to treatment.
Relapses and treatment resistance
Despite advances in therapies, relapses and treatment resistance remain significant challenges in treating metastatic melanoma. A relapse refers to the cancer returning after a period of remission. Treatment resistance occurs when a cancer does not respond to treatment or stops responding to a treatment.
Resistance can occur because tumors are not made up of identical cancer cells. This means a treatment can be effective at eliminating some of the cells in a tumor (or even most of the cells in a tumor), but not all. The surviving cells can continue to grow and replicate.
Cancer cells can also adapt when exposed to cancer therapies, modifying their behavior or undergoing genetic changes that enable some cells to survive. These adaptive responses can lead to drug resistance and relapse.
Keep in mind that cancer treatment, relapses, and resistance are complex topics, and that this is a simplified explanation. Also keep in mind that there are other reasons a person may need to discontinue treatment or change their approach to treatment, such as side effects.
Coping when cancer does not respond to treatment
Experiencing a setback like drug resistance or a relapse can be frustrating. Here are a few strategies that may help as you navigate the next steps in treatment.
- Talk to your healthcare team. Be honest about any concerns, fears, and frustrations. Ask them to explain what they do and do not know about why initial treatment was ineffective.
- Ask about possible next steps in treatment. Are there drugs that might be more effective? Should you consider a clinical trial or tumor-infiltrating lymphocyte therapy? Are there additional tests you need before making your next treatment decision? What side effects and risks need to be considered?
- Seek a second opinion. Getting a second opinion from another healthcare provider or team can be helpful as you navigate your next treatment decisions.
- Focus on mental health and social support. Counselors, oncology social workers, and support groups can be helpful when processing a setback. Also make time for the important people in your life and the things you enjoy.
When in doubt, talk to your healthcare team. They are there to support you. They are there to help you navigate all steps in diagnosis and treatment.
Sources: NCI Dictionary of Cancer Terms. Metastas... + 8
- NCI Dictionary of Cancer Terms. Metastasis. Accessed July 30, 2026.
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- American Cancer Society. Treatment of Melanoma Skin Cancer, by Stage. February 21, 2024.
- Sawsan Sudqi Said and Wisam Nabeel Ibrahim. Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives. Pharmaceutics, 2023. Vol. 15, No. 4.
- Alice Soragni, Erik S. Knudsen, et al. Acquired resistance in cancer: towards targeted therapeutic strategies. Nature Reviews Cancer, 2025. Vol. 25, No. 8.
- Edward Winstead. Strategy May Prevent Tumor Resistance to Targeted Cancer Therapies. National Cancer Institute. March 17, 2023.
- AIM at Melanoma Foundation. You’re Not Out of Options: What to Do When First-Line Melanoma Treatment Fails. November 11, 2025.
- Mayo Clinic. When cancer returns: How to cope with cancer recurrence. January 21, 2026.
- American Cancer Society. If Cancer Treatments Stop Working. July 31, 2025.
