AEG-1 protein blocks the effects of retinoic acid in the leukemia and liver cancer -
Retinoic acid is a form of vitamin A that is used to treat and help prevent the recurrence of a variety of cancers, but for some patients, the drug is ineffective. The reason for this resistance was uncertain until this week when researchers from Virginia Commonwealth University (VCU) Massey Cancer Center have shown that a protein called AEG-1 blocks the effects of retinoic acid on leukemia and liver cancer. Because AEG-1 is overexpressed in most cancers, these findings could impact the care of countless cancer patients.
Study details were published this week in the online edition of the journal Cancer Research , a journal of the American Association for Cancer Research. The team of scientists led by Devanand Sarkar, M.B.B.S., Ph.D., has shown that AEG-1 protein binds to retinoid X receptors (RXR), which help regulate cell growth and development. RXR is usually activated by retinoic acid, but overexpressed AEG-1 protein in cancer cells block these signals and help promote tumor growth. Using complex animal models, researchers have shown that blocking the production of AEG-1 has retinoic acid for deeply kill cancerous liver cells.
"Our results are the first to show that AEG-1 interacts with the retinoid X receptor," said Sarkar, Harrison Scholar at VCU Massey Cancer Center, Blick Scholar and Associate Professor in Human and Molecular Genetics Department member of the VCU Institute of molecular medicine (VIMM) at VCU School of medicine. "This research has immediate clinical relevance such as doctors could start patients screening for cancer AEG-1 expression levels in order to whether retinoic acid should be prescribed. "
Sarkar and his colleagues studied AEG-1 for years. They were the first to create a mouse model demonstrating the role of AEG-1 in liver cancer, and they have been actively working to develop targeted therapies that block AEG-1 production. This study expanded their knowledge of the molecular interactions of AEG-1.
"We continue to test combination therapies involving AEG-1 and inhibition of retinoic acid in animal models, and early results are promising," said Sarkar. "If we continue to see these results in more complex experiences, we hope to eventually propose a phase 1 clinical trial in patients with liver cancer. "
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