After struggling slightly with the immensity of the task at hand, we (my supervisor(s) and I) have decided to delineate the project slightly more clearly: instead of studying important cancer pathways as they occur in fibroblasts (cells that mainly serve structural purposes in the body and are involved in wound healing), the research will now focus on modelling pathways involved in skin cancer. In particular, the evolution of skin cancer from initial benign states to primary and subsequently metastatic disease (melanomagenesis) will be modelled. Hopefully the work will provide some insight into how melanoma could be treated more effectively.
At the moment, although effective therapies do exist to treat melanoma, the patients almost inevitably relapse after a while, due to resistance to the drugs. The following images (from Wagle et al. (2011)) are not for the faint-hearted. This patient had advanced metastatic melanoma:
He was treated with a drug that inhibits one of the main “drivers” of the tumours (a protein kinase, which is constitutively activated), and the nodules entirely disappeared:
However, a couple of months later the tumours re-emerged and this time they were resistant to the drug. The man died a few weeks later.
A better understanding of the pathways involved in melanomagenesis and drug resistance mechanisms may be able to inform future therapy options. Better treatment may mean that we can pre-empt these relapses and prevent them from occurring.
Wagle N, Emery C, Berger MF, Davis MJ, Sawyer A, Pochanard P, Kehoe SM, Johannessen CM, MacConaill LE, Hahn WC, Meyerson M, Garraway LA (2011) Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling. Journal of Clinical Oncology 29: 3085-3096