The genetic and molecular understanding of melanoma, and the changes in therapy, are currently in the midst of transformation. Technology is now possible to obtain the sequencing of melanoma genes with their mutations and tumor-promoting mechanisms. Recently significant progress in the molecular mechanisms of melanoma in the relationship to the melanoma cells and immune system showed great promise.

Over the last ten years, 11 new novel drugs and combination regimens have been approved by the FDA. These drugs are placed in two categories. The first is immunotherapy, and the second is targeted therapy. We now know that long-term tumor remission is achieved using checkpoint inhibitors. The good news is that the clinical responses to the new targeted therapies are remarkable in helping patients with metastatic melanoma stage IV. With further genomic analysis, we can now produce a durable response with minimal toxicities and more patients.

Malignant melanoma if the six most common US cancer diagnosed. The actual incidence of melanoma is increasing more rapidly than not of any other malignancy. Many studies support that the etiology is from ultraviolet radiation. For example, my grandmother suffered it at the age of 95, and my uncle had it at the age of 40. They were fair white-skinned and had sun exposure.

Understanding the genetic makeup of melanoma has become the cornerstone of advances in the management of stage IV metastatic disease. We now perform genetic analysis that focuses on driver genomic aberrations. It is now the standard of care. Not only can we evaluate BRAF mutations, but we can also evaluate several other up-regulated mutations in melanomas. It is of utmost importance to focus on blocking genes at several points. These drive cancer and cause it to spread. Testing is individualized and personalized. Finding out what drives your cancer is of utmost importance.

In the past decades, we have learned that several signaling pathways drive melanoma progression. These include the MAPK kinases. Approximately 70% of melanomas carry genetic mutations of the kinases in these pathway, such as BRAF and MEK. We now have small molecular inhibitors or antibodies that block these pathways. These mutations lead to the uncontrolled proliferation of cancer. By blocking them, you can slow cancer growth. Therefore, testing is essential.

Immunotherapy breakthrough drugs show long-term tumor inhibition. These checkpoint inhibitors increase a patient’s immune system.

T-cell mediated therapy is powerful. We are now also performing adoptive T-cell transfer with CART therapy.