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.

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 https://www.bethyl.com/category/c-Myb_3/. 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.