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ACCRF Research Update
October 2013
In This Issue

LandscapeLandscape of ACC Research
In October 2006, ACCRF drafted its first Research Agenda, outlining the foundation's guiding principles and highlighting the key areas for directed research. Seven years later, many of the original objectives have been accomplished and tantalizing new questions have arisen. Accordingly, the ACCRF Scientific Advisory Board recently undertook a review of the key past research findings and discussed the future research priorities for the field of ACC research and the foundation. The result of these deliberations is a new working document The Landscape of ACC Research: Past, Ongoing and Future Explorations. Ideally, the document will benefit from the continuing input of a wide range of interested parties and will serve as a useful map for researchers seeking fruitful avenues to pursue.
 OrphandrugaccOrphan Drug Designation for Dovitinib in ACC

On September 26, 2013, the U.S. Food and Drug Administration granted an orphan drug designation to dovitinib for the treatment of patients with ACC. Dovitinib is an oral drug being developed by Novartis Pharmaceuticals that targets FGFR as well as various other molecules, including VEGFR and PDGFR. This represents the first ever orphan drug designation for ACC.


Orphan drug designation does not indicate that the drug has been submitted for regulatory approval or found to be effective in treating a disease. Rather, it qualifies the sponsor of the drug for various investment incentives to develop the drug for a rare disease like ACC. The process requires the submission of supporting materials that provide a mechanistic rationale for, and preliminary data on, the potential efficacy of the drug in the particular disease.  An orphan drug designation does not guarantee that dovitinib will be commercially available. 


Supported by ACCRF, researchers at the University of Virginia and South Texas Accelerated Research Therapeutics (START) were instrumental in generating the supporting materials, including both preclinical and clinical findings. Preliminary clinical results included 2 patients with partial responses (tumor shrinkage) among 19 evaluable patients with previously progressing disease. Four patients had progressive disease within 4 months of starting treatment, 9 patients had stable disease for more than 6 months, and 6 patients had stable disease but had not yet been followed for 6 months at the time of the June report. Dovitinib was shown to have a tolerable safety profile in these patients. Additional results from clinical trials in Virginia, Korea and Canada should be available in the coming year.

MYBconfInternational MYB Conference

Recent research findings have elevated the importance of the proto-oncogene MYB. Approximately 70% of ACC tumors harbor a rearrangement of MYB and even more involve MYB over-expression. In addition, studies have identified genetic alterations in MYB in significant subsets of leukemia and pediatric brain tumors. Given this context, ACCRF was very pleased to sponsor the International MYB Conference organized and hosted by Dr. Scott Ness at the University of New Mexico.  


The conference took place July 22-23 in Albuquerque, NM, with more than 40 researchers in attendance. Speakers included Joseph Lipsick (Stanford), Robert Ramsay (Melbourne), Timothy Bender (Virginia), Bruno Calabretta (Thomas Jefferson), Thomas Gonda (Queensland), Göran Stenman (Gothenburg), Diana Bell (MD Anderson), Christopher Moskaluk (Virginia), Timothy Chan (Memorial Sloan-Kettering), Carlos Caulin (MD Anderson), Karl-Heinz Klempnauer (Muenster), Michael Wick (START), Larry Sklar (New Mexico), John Bushweller (Virginia), Georg Leutz (Humboldt), Jon Frampton (Birmingham) and Arturo Sala (Brunel).


The conference brought together MYB biologists and disease experts to discuss novel therapeutics targeting human MYB proteins. The main goal was to facilitate and promote collaborations and, indeed, ACCRF already has received research proposals that grew out of conference discussions.
MYBantisNew MYB Antibodies for Research

Many MYB antibodies are commercially available and some perform well for immunohistochemistry and western blotting. However, researchers have struggled to find MYB antibodies that bind with sufficient affinity for use in chromatin immunoprecipitation sequencing (ChIP-seq), an important method for identifying which portions of DNA are bound by a given protein and, therefore, may be downstream targets.


As part of their ACCRF-funded project at Massachusetts General Hospital to study the chromatin landscape of MYB in ACC, Drs. Bradley Bernstein and Birgit Knoechel tested many MYB antibodies and found only one that worked on their ChIP-seq platform. Unfortunately, the antibody binds to a portion of the MYB protein (the C-terminus) that is lost in about 70% of ACC cases due to MYB's fusion with NFIB or another gene. Accordingly, Bethyl Labs was approached by Dr. Bernstein and ACCRF to develop new rabbit polyclonal antibodies that bind to a region within the first 7 exons of MYB as that region almost always is conserved in MYB-fusion-positive ACCs.


Bethyl Labs recently tested and made available five new MYB antibodies at One of the antibodies (catalog number A304-136A) performed well in ChIP-seq experiments and it recognizes an epitope coded within exon 6 of MYB, making it appropriate for studying most ACCs with MYB fusions.


Prior to the development of Bethyl Labs' new antibodies, Dr. Knoechel kindly provided a summary of commercially available MYB antibodies. Researchers should note that the same antibody may be offered by multiple companies.

The National Institute of Dental and Craniofacial Research (NIDCR) is part of the National Institutes of Health (NIH) and is charged with supporting research to improve oral health. NIDCR has a longstanding interest in both salivary glands and cancers of the head and neck, making the institute a natural and very effective ally of ACCRF.  Occasionally, we will be highlighting NIDCR-supported research that may be of interest to the ACC community.


Perhaps the most widespread side effect of head and neck cancer patients is dry mouth (xerostomia), usually the result of radiation treatments. Scientists supported by NIDCR have delved into the potential reasons for the lost function of salivary glands that leads to xerostomia. And they have explored ways to offset the effects of radiation, managing to preserve saliva production by more than 50% in treated mice compared with untreated mice. Hopefully, these findings can lead to better treatments and outcomes for head and neck cancer patients with a method that is temporary, doesn't involve viruses, and is localized to the salivary glands. More details are available at 

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