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.
This treatment includes surgery, radiation, or adjunct systemic therapy with immunotherapy with checkpoint inhibitors, various cancer autologous vaccines, dendritic vaccines, and oligonucleotides, and chemotherapy. New molecular genomic testing is essential.
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.
We are now able to evaluate circulating cancer cells. These are cells causing metastasis that predict remission and prognosis. The higher their level is, the more aggressive your treatment needs to be. This liquid biopsy is essential in stratifying risk. Monitoring circulating tumor DNA cells during treatment for advanced melanoma can benefit in identifying those patients likely to benefit from treatment with targeted therapies. These evaluations were reported in the ASCO annual meeting. “Our study offers firm evidence that tracking this genetic information may help identify patients who survive longer as a result of combination drug regimes“ Circulating cancer cells were measured by pre-and posttreatment. Lactic dehydrogenase was also a marker used and a risk factor and staging factor. Additionally, analysis of circulating cancer cells has been valuable in differentiating between progression and hyper progressive pseudo-disease in patients on checkpoint inhibitors.
We are now able to find out which chemotherapy is most effective in your cancer and which natural substances work best. Low dose metronomic chemotherapy is used, which avoids the toxic side effects of maximum traditional tolerated dose chemo. Lower doses of chemotherapy also do not cause chemotherapy resistance and immunosuppression. Natural substances are non-toxic and work through multiple mechanisms to inhibit cancer growth.
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.
Tumor vaccines are available for use in melanoma—the Whole-cell vaccines with the use of dormant autologous cells and dendritic cell vaccines used. Supportive oligonucleotide (SOT) is another nontoxic therapy.
The patient’s underlying immune system is optimized. It is of critical importance and your overall treatment program.
We now have rapid advances in new therapies in patients with metastatic melanoma. We are currently performing chemosensitivity testing to find out which chemotherapy works. I am involved with low dose metronomic chemotherapy without the toxicities of standard maximum tolerated dose chemotherapy. Testing is done for natural substances to evaluate the effectiveness of the treatment of melanoma. Testing for 72 genetic “biomarkers,” performed, which are pathways feeding your cancer, and they are blocked.
Various forms of immunotherapy, including the checkpoint inhibitors, autologous cancer vaccines, dendritic cell vaccines, and supportive oligonucleotides (SOT), are a combination solution for the treatment of Melanoma. The immune function of the patient is evaluated and optimized, allowing for the best possible result.
If you would like further information concerning your melanoma case, please contact me at 480-361-7020.