Date

2013

Document Type

Thesis

Degree

Master of Science

Department

Molecular Biology

First Adviser

Iovine, Kathryn

Abstract

Melanoma is the most lethal type of skin cancer and originates in melanocytes, cells that produce the pigment melanin. Five year survival rates are particularly high for this type of cancer if the tumor is diagnosed and treated early. However, survival rates decline significantly if the tumor is allowed to metastasize. Frequency of melanoma has risen over recent years, especially in young people. Much progress has been made in treating melanoma; however, tumor recurrence is frequently seen in patients after treatment has concluded. The leading genes that are found to be mutated in melanoma are v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and cyclin dependent kinase inhibitor 2A (CDKN2A) which belong to the MAPK (Mitogen-activated protein kinase/Extracellular signal-regulated kinases) pathway, the phosphoinositide 3' kinase (PI3K)/AKT pathway or the INK4/ARF locus. Together, these two pathways and locus form a signaling network that work in tandem to promote cell proliferation, migration, invasion and metastasis. Recent breakthroughs in treating melanoma include the advent of BRAF inhibitors, but patients often experience tumor recurrence. Research conducted to understand acquired BRAF inhibitor resistance suggests that tumor regrowth is due to continued activation of the MAPK and PI3K/AKT pathways through BRAF independent routes. Therefore, new treatments, which can be personalized, are being developed that target multiple components of both of these pathways. The epigenetic causes of melanoma are vast and are just recently becoming clear.

Share

COinS