Tom Graeber, Ph.D.
June 05, 2012 - The Melanoma Research Alliance (MRA), the largest private funder of melanoma research, today announced that 22 researchers at leading academic research institutions around the world have been awarded grants to develop improved means to prevent, detect and treat deadly skin cancer.
Among the areas of investigation being pursued by MRA’s 2012 award recipients is the critical effort to advance existing therapies for metastatic melanoma, including the recently FDAapproved vemurafenib (for patients with BRAF mutant melanoma) and ipilimumab (an immunotherapy), which have extended the lives of some patients and ignited new optimism in the field of melanoma research. The aim of several of MRA’s new grants is to prolong the effects of these approaches, including identification of resistance mechanisms and new biomarkers and testing drug combinations. Additionally, several of the grants are focused on finding new drug targets for those patients whose cancers are not driven by mutant BRAF (about 50% of all melanomas).
Thomas G. Graeber, Ph.D., University of California, Los Angeles
Delineating BRAF inhibitor resistance mechanisms using proteomic profiling
An exciting advance in cancer therapies has been the development of drugs that specifically target the function of mutated genes. Regression of tumors targeted by these drugs has been remarkable. Drugs targeted at inhibiting the BRAF mutation in certain melanomas have led recent news headline reports due to spectacular tumor regression. Because of the specificity of these 'molecularly targeted' drugs, they have fewer clinical side effects. Unfortunately, most patients develop drug resistance in less than a year, and this traumatic aspect has also led news headlines. Cancer is a complex mix of interconnected events gone awry through mutations. We know much about the individual events, but we need a better understanding of how they function together, as a system, to cause malignancy. The future of molecular therapies relies on targeting multiple events, thus making it exponentially more difficult for tumor cells to gain the multiple mutations required to escape this coincident drug assault. This is somewhat analogous to anti-HIV drug cocktail therapies. In our work, we use technologies that concurrently measure thousands of events within cancer cells. In particular, we use mass spectrometry-based 'proteomics' to measure the activity of signaling proteins that drive aberrant tumor cell growth and survival. We then analyze the data using computational algorithms to identify points of susceptibility in the system. We are applying this approach to build a 'systems biology' perspective of how melanoma cells become resistant to BRAF inhibitors. These studies have broader implications since the BRAF V600E mutation occurs in 7% of all cancers.
Complete list of 2012 MRA award recipients
Read the MRA News Release of April 24, 2012