RESISTANCE DEVELOPMENT AND THE EFFECT OF PALBOCICLIB TREATMENT ON VEMURAFENIB AND DABRAFENIB RESISTANT BRAF MUTANT MALIGNMELANOMA CELL LINES
Project no. 68 · Status: Kapanmış · 2017
Summary
Malignant melanoma is the most common form of cancer in which the mutation is seen in BRAF genes. 91% of these mutations are V600E gene mutations. Emerging BRAF somatic mutations induce tumorigenesis. Vemurafenib (VEM) is the first BRAF inhibitor approved by the FDA in 2011 for use in BRAF-V600E gene mutant malignant melanoma patients. However, clinical studies have shown that malignant melanoma with BRAF mutation develops 50% vemurafenib resistance and causes a decrease in response to treatment. Dabrafenib (DAB) is a BRAF inhibitor manufactured as an alternative to Vemurafenib, approved by the FDA in 2013 for the treatment of metastatic malignant melanoma patients carrying the V600E or V600K mutation. In this project, activation / inhibition changes in MAPK, mTOR and PI3K / AKT pathways in melanoma cells resistant to DAB and VEM were investigated. In addition, Palbociclib was applied to resistant cells, cell viability, cell cycle phases and apoptosis were evaluated and the effect of Palbociclib on defeating VEM resistance was investigated.