Radiosensitization by modulating inhibitors of apoptosis

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R41CA112812-01
Agency Tracking Number: CA112812
Amount: $106,000.00
Phase: Phase I
Program: STTR
Awards Year: 2005
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
Ascenta Therapeutics, Inc., 28202 Cabot Rd, Ste 200, Laguna Niguel, CA, 92677
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (734) 615-7017
Business Contact
Phone: (619) 299-1550
Research Institution
ANN ARBOR, MI, 48109
 Nonprofit college or university
DESCRIPTION (provided by applicant): Radioresistance markedly impairs the efficacy of tumor radiotherapy and involves anti-apoptotic signal transduction pathways that prevent radiation-induced cell death. The inhibitors of apoptosis proteins (IAP) are important intrinsic cellular inhibitors of apoptosis, highly expressed in prostate and lung cancer cells, and play an important role in resistance to apoptosis induced by chemo/radiotherapy. Through computational structure-based 3D-database searching and rational design, a series of small molecule inhibitors of IAP have been discovered that showed promising therapeutic activity and specificity to overcome apoptosis-resistance in vitro in cancer cells with high levels of IAP. The specific aim of this Phase I STTR project is to investigate radiosensitization potential of the small molecule IAP inhibitors in vitro and especially in vivo in nude mouse xenograft models of human cancers of prostate and lung. The proposed studies will test the hypothesis that inhibition of anti-apoptotic activity of IAP by small molecule IAP inhibitors will overcome radioresistance and restore sensitivity of cancer cells to ionizing irradiation. The success of this Phase I STTR project will pave the way to Phase II STTR, aiming to develop the most potent small molecule inhibitor of IAP as a novel, molecular targeted approach for radiosensitizing human cancers with high levels of IAP, and as an entirely new class of anticancer therapy.

* Information listed above is at the time of submission. *

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