Our lab is interested in why current generation treatments for melanoma fail, so that we can design rational approaches to improve them. This research falls into two major categories:
1. Targeted therapies, such as BRAF inhibitors. We have demonstrated that BRAF inhibitors not only induce cytotoxic pathways in melanoma cells, but also induce pathways that paradoxically promote survival (for example, Haq et al, Cancer Cell (2013)). We are characterizing these â€œadaptive resistanceâ€ pathways at a deep molecular level, so we can develop combinatorial approaches to overcome this resistance. Our comprehensive surveys suggest that this form of resistance is ubiquitous in melanoma and in virtually all other cancer types.
2. Immunotherapies. We have recently developed new models to evaluate resistance to immunotherapy. Using these approaches, we have designed comprehensive screens to identify mechanisms of innate resistance to immunotherapies such as PD-1/PD-L1 inhibitors and CTLA-4 checkpoint inhibitors. Characterizing candidate resistance pathways at a molecular level will lead, it is hoped, to the development of strategies to improve these treatments using combinations of small molecules and immunotherapies.