Hypolipidemic dehydroacetic acid (DHAA) treatment to prevent growth of BRAF V600E positive tumors.
Up to 50% of melanoma cases harbor the BRAF V600E mutation, which is also a contributing factor in other cancer types such as, colorectal cancer, hairy cell leukemia, and multiple myeloma. Treatment strategies for melanoma include surgical removal of the tumor and surrounding area followed by chemotherapy and immunotherapy. These therapies are often successful; however, some mutations associated with melanoma are sensitive to the patient’s diet. There is a need for therapeutic strategies that address these diet sensitive forms of melanoma.
BRAF is a serine/threonine- protein kinase and a proto-oncogene that promote cell growth by initiating the MAP kinase signaling cascade. BRAF V600E mutations are known to enhance the tumorigenicity of melanoma. Hypolipidemic agents, such as dehydroacetic acid (DHAA) competitively bind the BRAF V600E mutant protein without initiating the MAP kinase signaling cascade. Emory inventors demonstrated that DHAA significantly reduced tumor size in an animal model of melanoma without any observed toxicity. DHAA is currently used in cosmetics and as a food preservative and could be repurposed as a hypolipidemic for use in cancer therapeutics. DHAA has potential for use in other BRAF V600E positive forms of cancer.
DHAA is a compound that has been tested in vitro and in vivo in a mouse model.
Publication: Xia, S. et. al. (2017) Cell Metabolism, 25(2), pp358-373.