By Yolanda Smith, BPharm
There is a considerable amount of scientific research on the subject of melanoma development and treatment, which has progressed particularly rapidly in recent decades.
The MITF gene is considered 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 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.
The National Cancer Institute (NCI) 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 utilises tumor-infiltrating lymphocytes (TILs), which are isolated from the tumor and then grown in a laboratory culture. The can then ne readministered to a patient following a treatment to reduce the concentration of T cells in the body.
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 of the metastatic melanoma and induce apoptosis.
There has also been some interest in a vaccination to boost the ability of the immune system to fight the abnormal cancerous cells of melanoma.
A mutation in the B0Raf gene has been identifies in approximately 60% of melanomas, which may present a via treatment target for the future.
Initial trials of B-Raf inhibitors such as vemurafenib suggested a positive response in most patients that exhibit the gene mutation, which was confirmed by successive studies in 2011. The led to the FDA approval for the drug later that year, indicated for advanced melanoma.
Other B-Raf inhibitors such as dabrafenib have since been studied, with more effective results than patients with chemotherapy. As a result, 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 effect notably increased with the combination also.
Research studies have found administration with 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, in contrast to an 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 in use. Thus, 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 increase side effects and high cost to treatment.
In addition to pharmaceutical advances in research, there are some other methods that are being investigated for use in the treatment of melanoma.
High-resolution ultrasound scanning can aid in the surveillance of the metastatic melanoma and the involvement of lymph nodes. The SUNMEL trial focused on the utility of surveillance with ultrasound 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.
Last Updated: Nov 12, 2015