Facilitated By

San Antonio Medical Foundation

Efficacy Study Of Inecalcitol In Combination With Decitabine In Acute Myeloid Leukemia Patients Unfit For Standard Chemotherapy

Brooke Army Medical Center

Brooke Army Medical Center (BAMC) at Fort Sam Houston, Texas, is proud to provide safe, quality care to our military service members, their families, veterans and civilian emergency patients as the most robust and productive healthcare organization within the Military Health System (MHS).

Principal Investigator(s)
Email for information
Funded by
HJF
Research Start Date
Status
Active

Inecalcitol is a vitamin D receptor (VDR) agonist, a chemically modified analogue of calcitriol the active form of natural Vitamin D3. Inecalcitol is a novel synthetic vitamin D analogue developed by Hybrigenics. Inecalcitol was found to be 10 times more potent and 100 times less toxic than calcitriol. In addition to their well-known effects on calcium and phosphate homeostasis, calcitriol and VDR agonists are being increasingly recognized for their potent role in cell proliferation, differentiation, and immunomodulation. They exert their activity through both genomic and non-genomic pathways. The genomic activity is mediated through the VDR, a member of the steroid hormone receptor superfamily. Ligand binding induces conformational changes in the receptor, its heterodimerization with the retinoid receptor, and interactions with coactivator proteins, resulting in histone modification at specific gene promoter sites (vitamin D response elements) and transcription of target genes. Detection of the VDR in many normal tissues and cancer cells led to consider their possible use for various therapeutic applications such as disorders of the immune system, hormone secretion, cell differentiation or cell proliferation. Combined use of decitabine (a demethylating agent) and inecalcitol results in a potent activation of VDR signaling pathway which limited leukemia progression and abolished the clonogenic potential of leukemic initiating cells. Therefore, association of demethylating agent with inecalcitol would improve the efficacy of these agents in AML.

Collaborative Project
Clinical Care
Cancer
The appearance of name-brand products in this article does not constitute endorsement by Brooke Army Medical Center, the U.S. Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, the Department of Defense, or the U.S. Government of the information, products, or services contained therein.