The Importance of RAS Effectors
Mutational activation of RAS genes is detected in approximately 25 percent of human cancers. However, to date, activated RAS oncoproteins remain intractable pharmacological targets. Research in the McMahon Lab focuses on the importance of RAS effectors, such as the RAF family of protein kinases and phosphoinositide 3’ (PI3’)-kinases in the aberrant physiology of cancer cells.
To do so, the lab employs genetically engineered mouse (GEM) models of human cancer, patient-derived xenografts (PDXs) and cultures of cancer cells in combination with various genetic or pharmacological to explore how signaling pathways contribute to cancer cell initiation, progression, and response to therapy.
McMahon Lab Translational Cancer Research Program
The McMahon lab’s translational cancer research program focuses on the mechanisms underlying the development of metastatic melanoma, lung, and thyroid cancer. Although these malignancies are derived from distinct cell types, they share a striking number of common genetic alterations especially activating mutations in KRAS, BRAF, PIK3CA, or CTNNB1 (b-catenin).
In addition, many of these tumors display alterations in tumor suppressors such as CDKN2A, PTEN or TP53. To do this, Dr. McMahon’s laboratory works with cultured human cancer-derived cells and with genetically engineered mouse models of human cancer. Such model systems have demonstrated considerable value in the design and evaluation of new diagnostic, prognostic, and therapeutic tools to treat patients with cancer.