Protein Blocks Effects of Cancer Fighting Vitamin A Drug

Devanand Sarkar, M.B.B.S., Ph.D Harrison Scholar at VCU Massey Cancer Center, Blick Scholar and Associate Professor Department of Human and Molecular Genetics Member of the VCU Institute of Molecular Medicine Virginia Commonweath School of MedicineMedicalResearch.com Interview with:
Devanand Sarkar, M.B.B.S., Ph.D
Harrison Scholar at VCU Massey Cancer Center,
Blick Scholar and Associate Professor
Department of Human and Molecular Genetics
Member of the VCU Institute of Molecular Medicine
Virginia Commonweath School of Medicine

Medical Research: What are the main findings of the study?

Dr. Sarkar: Retinoic acid (Vitamin A) is an anti-cancer drug for a number of cancers including liver cancer. However, all patients do not respond to retinoic acid. Astrocyte elevated gene-1 (AEG-1) is overexpressed in a large percentage of cancer patients and promotes development and progression of cancer. In this study we document that AEG-1 inhibits retinoic acid function. Combinatorial strategy involving AEG-1 inhibition and retinoic acid synergistically blocks growth of human liver cancer cells in animal models.

Medical Research: Were any of the findings unexpected?

Dr. Sarkar: Retinoic acid functions by interacting with a receptor complex involving retinoid X receptor (RXR) and retinoic acid receptor (RAR). Our study reveals that AEG-1 interacts with RXR and by that way blocks retinoic acid function. This is a novel aspect of AEG-1 that has not been documented before.

Medical Research: What should clinicians and patients take away from your report?

Dr. Sarkar: Our results indicate that before starting retinoic acid therapy to cancer patients the patients should be screened for AEG-1 expression level. Patients with high AEG-1 expression may not respond to retinoic acid and in those patients a combination of retinoic acid and AEG-1 inhibition strategy might be more useful.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Sarkar: These studies might lead to a Phase I clinical trial evaluating combination of AEG-1 inhibition and retinoic  acid for cancer. Right now small molecule inhibitors of AEG-1 are not available. Future studies involve developing chemical inhibitor of AEG-1 as well as exploiting innovative ways to genetically inhibit AEG-1. RXR not only regulates retinoic acid function but also regulates functions of several other hormone, vitamins and lipids. Since AEG-1 interacts with RXR it might affect the functions of these molecules as well. Future studies aim at dissecting the role of AEG-1 in regulating endocrine and metabolic functions which might unravel novel functions of AEG-1 in diseases associated with these systems.

Citation:

Jyoti Srivastava, Chadia L. Robertson, Devaraja Rajasekaran, Rachel Gredler, Ayesha Siddiq, Luni Emdad, Nitai D. Mukhopadhyay, Shobha Ghosh, Phillip B. Hylemon, Gregorio Gil, Khalid Shah, Deepak Bhere, Mark A. Subler, Jolene J. Windle, Paul B. Fisher, and Devanand Sarkar. AEG-1 Regulates Retinoid X Receptor and Inhibits Retinoid Signaling. Cancer Research, 2014; DOI: 10.1158/0008-5472.CAN-14-0421