Development of an Oncogene-Targeted Therapeutic

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$271,227.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41CA141908-01
Award Id:
93599
Agency Tracking Number:
CA141908
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
PHOENICIA BIOSCIENCES, INC., 233 NEEDHAM ST, STE 300, NEWTON, MA, 02464
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
808428689
Principal Investigator:
DOUGLAS FALLER
(617) 638-4173
DFALLER@BU.EDU
Business Contact:
SUSAN PERRINE
() -
Research Institution:
BOSTON UNIVERSITY MEDICAL CAMPUS

BOSTON UNIVERSITY MEDICAL CAMPUS
85 East Newton Street, M-921
BOSTON, MA, 2118

Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): The concept of targeting cancer therapeutics towards specific mutations or abnormalities in tumor cells which are not found in normal tissues has the potential advantages of high selectivity for the tumor and correspond ingly low secondary toxicities. At least 30% of all human malignancies display activating mutations in the p21Ras genes, and perhaps another 60% display other activating mutations or over- activity of p21Ras-signaling pathways. We previously discovered tha t over-activity of p21Ras signaling sensitizes tumor cells to apoptosis induced by suppression of PKC? activity, which is not toxic to cells with normal levels of p21Ras activity. This property, designated Ras-mediated apoptosis , can be exploited as a ta rgeted cancer therapeutic. We have characterized Ras-mediated apoptosis molecularly, demonstrated its selectivity in vitro and in vivo, identified the specific target PKC isozyme (PKC?), identified two lead compounds for inducing cell death in tumors conta ining activated Ras or Ras pathways, and gained intellectual property protection on Ras-mediate apoptosis as a therapeutic. In this Phase I STTR application, we will refine and explore Lead Compound I by generating specific analogs, and use in vitro and in vivo studies to select the optimal inducer of Ras-mediated apoptosis. Assays will include assessment of PKC? specificity, targeting of cytotoxicity for cells expressing an activated Ras protein, and xenograft tumor models. We will then move this compound forward into formal preclinical studies. PUBLIC HEALTH RELEVANCE: Mutation or activation of Ras or Ras-directed signaling pathways occur in up to 70% of human malignancies, and the applicant organization has developed a therapeutic strategy by which progra mmed cell death can be induced in tumors with activation of Ras or Ras pathways. This Phase I STTR proposal is to carry out further preclinical testing of the current lead drug candidate, and analogs of this compound, to select the optimal compound to move into clinical trials. Successful development of this therapeutic could allow normal survival of many patients who would otherwise die of their disease, and could reduce annual medical care costs by billions of dollars.

* information listed above is at the time of submission.

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