Immunotherapy treatments, which stimulate the immune system to kill cancer cells, have revolutionized the treatment of melanoma. An example of immunotherapy is immune checkpoint inhibitors (ICIs), which are commonly used to treat melanoma. However, about half of patients will either not respond to ICIs (primary resistance) or they will respond for a short time and then stop responding (secondary resistance).1 Primary and secondary resistance is also common for patients whose tumors have BRAF mutations and who receive a type of targeted therapy called BRAF/MEK inhibitors.2
MRA has a long-standing interest in research studying treatment-resistant disease. With support from MRA, researchers are investigating strategies aimed at overcoming resistance, extending patients’ response to treatment, and identifying factors that may predict how patients will respond to treatment.
Biomarkers, which are biological factors that can be measured, can be used to predict how patients will respond to different treatments. This would allow healthcare providers to know if a certain treatment is a good option for each patient, before the treatment is given.
(+) Biomarkers can be identified through changes in the DNA or differences in how immune cells are working, and they can even be stress related. MRA-funded researchers are studying biomarkers to predict who will respond to different treatments. Additionally, MRA-funded researchers are also working to identify biomarkers that may predict which patients are more likely to experience side effects from immunotherapy. When biomarkers are used to identify patients who are less likely to respond to ICIs or who may experience difficult side effects, the patients could then be treated with other treatments instead.
In addition to ICIs, researchers are also studying new treatments for melanoma in the laboratory and in clinical trials.
Since there are several approved therapies to treat patients with melanoma, researchers are also studying different combinations of treatments, and new ways to give treatments to patients.
An emerging area of study is looking into whether giving therapy before surgery (neoadjuvant) may be more effective than giving treatment after surgery only. Studies have shown that patients with BRAF-mutated metastatic melanoma, treated with the ICIs, nivolumab and ipilimumab, followed by BRAF/MEK inhibitors upon progression provided better 2-year overall survival than the reverse treatment.3
MRA-funded investigators are actively studying the reasons that lead to treatment resistance. By developing new therapies—or new combinations of therapies—and identifying factors that can predict which patients will respond to current treatments, patients with melanoma will have better treatment options that will lead to longer responses, fewer side effects, and improved survival.
