There is a considerable amount of scientific research on the subject of melanoma development and treatment, which has progressed rapidly over the past several decades.
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Pathophysiology
The MITF gene is believed to play an important role in the pathogenesis of melanoma, as it is responsible for the production of the transcription factor that synthesizes melanin.
Studies have shown that ultraviolet (UV) radiation may lead to an alteration in the p53 transcription factor and increased production of melanocyte-stimulating hormone (MSH), which binds to melanocortin 1 receptors (MC1R) and increases the expression of MITF. This provides a potential target for specific therapies for melanoma.
Target therapies
The National Cancer Institute (NCI) in the United States is in the process of developing gene therapy and other novel treatments for use in the management of melanoma.
Adoptive cell therapy (ACT) is a technique that utilizes tumor-infiltrating lymphocytes (TILs), which are isolated from the tumor and then grown in a laboratory culture. Additionally, genetically altered autologous lymphocytes can be transferred to the patient to deliver genes that are responsible for the encoding of T cell receptors in the lymphocytes. These can be manipulated to target abnormal cells that are particularly harmful in metastatic melanoma and induce apoptosis.
There has also been some interest in developing a vaccine to boost the ability of the immune system to fight the abnormal cancerous cells of melanoma.
B-Raf inhibitors
A mutation in the B-Raf gene has been identified in approximately 60% of melanomas, which may present as a target gene for the development of future therapies.
Initial trials of B-Raf inhibitors such as vemurafenib suggested a positive response in most patients who exhibit the gene mutation, which was confirmed by successive studies in 2011. This data led the United States Food and Drug Administration (FDA) to approve the drug later that year for the treatment of advanced melanoma.
MOA Animation: Melanoma BRAF Inhibition
Other B-Raf inhibitors such as dabrafenib have since been studied, with more effective results found to arise as compared to melanoma patients treated with chemotherapy. As a result of these positive outcomes, dabrafenib was approved for use by the FDA in 2013.
The efficacy of B-Raf inhibitors may be improved if used in combination with other treatments, as the inhibition of multiple growth pathways may help to reduce the growth of cancerous cells. There has been some scientific evidence to support this notion; however, adverse effects were found to notably increase with the combination also.
Ipilimumab
Research studies have found that the administration of monoclonal ipilimumab increases the median survival significantly in patients with advanced melanoma, from 6.4 months to 10 months. Additionally, the survival rate at one year was increased for patients with ipilmumab therapy as compared to those treated with the experimental vaccine.
However, some researchers have questioned the credibility of this study, as the control group used an experimental vaccine, rather than a placebo or standard treatment currently being used. Therefore, further research is required in this area to confirm this suggestion.
Ipilimumab has also been evaluated in combination with dacarbrazine, which was associated with an increased median survival rate but also an increase in side effects and high cost to treatment.
Other methods
In addition to pharmaceutical advances in research, there are several other methods that are being investigated for use in the treatment of melanoma.
High-resolution ultrasound scanning can aid in the surveillance of metastatic melanoma and the involvement of lymph nodes. The SUNMEL trial focused on the utility of surveillance with ultrasound imaging to substitute invasive surgery that may not be required.
Additionally, oncolytic virotherapy is being considered as a future treatment option for melanoma in some countries. This technique uses oncolytic viruses to alter metabolism, anti-tumor immunity, and vasculature of the cancerous lesions.
References
Further Reading
Age-related fibroblast changes in males drive aggressive melanoma