In order to understand the science that is extremely specific to skin cancer, we must first understand that the ‘choosing’ of genes and turning them into proteins is a series of events that is known as a cellular signaling pathway. The genes that are switched on control migration (movement of cells) and proliferation (generation of new cells). Cells proliferate first, then migrate to a desired destination and differentiate in order to carry out a particular function.
The type of cells affected by skin cancer are melanocytes which are mainly found on the skin and in hair follicles, named after the pigment melanin which they release to protect the skin from UV rays. As I previously said in my book review of Extreme Survival, melanin is found in greater quantities in people with darker skin colours and smaller quantities in people with lighter skin colours. The chemical is made up of the amino acid tyrosine and is also responsible for the colour of one’s eyes.
The gene that melanocytes express is called BRAF which has the MEK/ERK pathway as its cellular signalling pathway. The pathway allows stimuli to be relayed so that cells can respond to changes in the environment, by migrating and proliferating.
In my earlier blog today, about cyclophosphamide, I described cancer as an uncontrollable division of cells. If the chemicals controlling proliferation, migration and differentiation are not released or are misregulated, melanoma (cancer of the skin) is caused. The most common cause of melanoma is the replacement of thymine with adenine in the DNA base sequence of a BRAF gene so BRAF proteins made have their amino acid valine is replaced by glutamic acid which means that their shape (tertiary structure) of the is changed. The shape is changed so the part of BRAF activating the pathway for the MEK/ERK proteins is always active. Therefore, cells are always proliferating (uncontrollably dividing). This forms a primary tumour.
Secondary tumours are made by the migration of the large number of new cells around the body in the lymph and blood, known as ‘metastasis’. These tumours are more dangerous and aggressive than the primary tumour as rapidly dividing cells could be moved to key areas for survival such as in the bones, brain and lungs.
Treatment of metastatic melanoma includes Vemurafenib which is a drug specifically targeting the mutated BRAF protein and works by switching of the MEK/ERK pathway, therefore preventing excessive proliferation. In order to use these drugs, a doctor must first sequence their patient’s genome to ensure that it is the specific mutation in the BRAF gene that is causing the cancer.