Why some melanoma patients are resistant to treatment
According to a study recently published in the Journal of Experimental Medicine, resistance to treatment of certain patients with melanoma may be due to a gene called TP63. Researchers at Queen Mary, University of London, have discovered that this gene is highly expressed in some melanomas and that these forms of melanoma are resistant to treatment. They hope that these findings will help them develop more effective therapies to treat this form of cancer.
Melanoma is diagnosed in about 13,000 people each year in the UK and the incidence of this type of cancer is increasing. Although among the other forms of skin cancer, melanoma is the least common, though this cancer has the highest mortality rate. This high mortality rate is due to dissemination that occur in early stages of the disease. It is estimated that about 2000 of skin cancer deaths are due to melanoma, which means 75% of all cancer dealths.
It should be noted that melanoma is difficult to treat if not eradicated in the early stages because of systemic dissemination. If advanced melanoma requires multimodal approach (chemotherapy, immunotherapy, surgery etc), in the early stages this cancer can be successfully treated by surgical excision and careful follow-up . Dr. Daniele Bergamaschi, a senior lecturer in cutaneous research at Queen Mary, said that in order to find more effective treatments of melanoma, one should understand the mechanisms that cause tumor cells to become resistant.
Researchers concluded that TP63 gene is associated with resistance to treatment after they analyzed 156 samples from 129 melanoma tissue. They found that the expression of p63 protein, which is encoded by the TP63 gene, is increased in more than 50% of samples. Dr. Bergamaschi said they did not expect to find this in the samples because p63 is a protein that is not usually found in melanocytes. It seems however that this gene become activated as the tumor begins to grow. In addition, researchers believe that the TP63 gene inhibits p53, a gene with implicated in apoptosis, that is programmed cell death. It should be mentioned that apoptosis is a natural mechanism by which cells die.
Based on these findings and on the possible implication that p63 protein may have in apoptosis pathway, researchers want to target this protein in order to develop more efficient treatments: “We therefore suggest that p63 should be considered when designing new treatments for melanoma which are focused on re-activating the apoptotic pathway in order to make the cancer cells easier to kill,” Dr. Bergamaschi said.