McGill University - Dankort Lab

Cancer represents a failure of built-in protection mechanisms to quell rogue cells that have sustained oncogenic mutations. RAS and BRAF are the two most prevalent mutated oncogenes found in human cancers, particularly in lung cancer (~30%) and melanoma (~85%) where they function in the Ras-activated Raf-Mek-Erk kinase pathway. Additionally, there is a constellation of tumour suppressor loss in these cancers; particularly losses in p53, PTEN, and INK4a/ARF. Despite the enumeration of genetic lesions from human cancer data, there remains a lack of understanding of how these oncogenes and tumour suppressors contribute to the evolution of malignancy. For instance, aberrant activation of the Ras-activated Raf-Mek-Erk pathway can paradoxically induce a sustained cell cycle arrest, suggesting additional genes cooperate to permit tumour formation and/or progression. Armed with the vast array of genetic and molecular tools afforded to those who work with the mouse as a model organism, our lab seeks to: (1) Define these cooperating genes and how they function (2) Establish when they are important in the evolution of a tumour and (3) Determine the proper cell to target for destruction within a tumor.