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Akt Inhibitors to Treat Ewing's Sarcoma

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
70560
Program Year/Program:
2004 / STTR
Agency Tracking Number:
CA102841
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Acenta Discovery, Inc.
Acenta Discovery, Inc. 9030 South Rita Road Tucson, AZ 85747
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2004
Title: Akt Inhibitors to Treat Ewing's Sarcoma
Agency: HHS
Contract: 1R41CA102841-01A1
Award Amount: $596,620.00
 

Abstract:

DESCRIPTION (provided by applicant): Novel drugs that improve overall survival with decreased morbidity are critical in the war on cancer. Acenta Discovery Inc. has partnered with the Toretsky Lab of the Lombardi Cancer Center to create and preclinically evaluate novel inhibitors of the protein Akt. An Akt inhibitor would have tremendous value in improving the lives of patients with many types of cancer and lead to a successful commercial venture. Akt modulated survival signaling enables tumors to survive cytotoxic chemotherapy. Inhibition of Akt signaling will reduce tumor survival thereby enhancing the effectiveness of cytotoxic chemotherapy by increasing apoptosis. This augmentation of cytotoxicity could be the difference between disease-free survival and relapse following a state of minimal residual disease. Since the recruitment of Akt to the cell membrane with phosphatidylinositol is critical for Akt to function, analogues of phosphatidylinositol have been developed that block Akt movement to the membrane without affecting the function of other lipid dependent molecules. We have a model of Ewing's sarcoma family of tumors (ESFT) that demonstrates Akt as critical for sensitivity to chemotherapy. In addition, clinical survival rates for patients with ESFT are poor, especially for patients with metastatic disease. It is well established that patients with ESFT often respond well to initial chemotherapy, however, relapse occurs at metastatic sites indicating that a subpopulation of tumor cells survived the initial cycles of therapy. One mechanism that could explain tumor cells surviving chemotherapy is the ability for IG F-I to activate survival pathways through Akt and avoidance of cell death. ESFT are known to rely on signaling through the insulin-like growth factor type I receptor (IGF-IR) for their survival (via Akt) and growth (via MAP kinase). Our previous work implicates PI 3-K and Akt as important survival molecules in ESFT. ESFT cells growing in spheroid culture demonstrate constitutively activated Akt. We hypothesize that Akt is a therapeutic target in patients with ESFT and that the development of clinical molecules that specifically block Akt function will improve patient survival. This proposal~ will evaluate a series of molecules that specifically block Akt function and determine if these molecules function to enhance chemotherapy effects in xenograft models of ESFT. Our findings from this Phase I Sun will hopefully lead to a key compound that can be further developed in a Phase II STTR ultimately leading to clinical trials in patients with ESFT.

Principal Investigator:

Jeffrey A. Toretsky
2026878655
JAT42@GEORGETOWN.EDU

Business Contact:

Hans Roth
5207997304
HANS.ROTH@ACENTADISCOVERY.COM
Small Business Information at Submission:

ACENTA DISCOVERY, INC.
9030 SOUTH RITA ROAD SUITE 300 TUCSON, AZ 85747

EIN/Tax ID: 371447259
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
GEORGETOWN UNIVERSITY
GEORGETOWN UNIVERSITY
Tucson, DC 20057
RI Type: Nonprofit college or university