Safety/Efficacy of Liposomal Reversan, a novel MRP1 modulator for Cancer Therapy

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$104,608.00
Award Year:
2009
Program:
STTR
Phase:
Phase I
Contract:
1R41CA137977-01
Agency Tracking Number:
CA137977
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
BUFFALO BIOLABS, LLC
BUFFALO BIOLABS, LLC, 73 HIGH ST, BUFFALO, NY, 14203
Hubzone Owned:
N
Socially and Economically Disadvantaged:
N
Woman Owned:
N
Duns:
830459546
Principal Investigator:
ARINDAM SEN
(716) 845-8911
ARINDAM.SEN@ROSWLLPARK.ORG
Business Contact:
LINDA WEBSTER
() -
lwebster@cbiolabs.com
Research Institution:
ROSWELL PARK CANCER INSTITUTE CORP

HEALTH RESEARCH INC. AND ROSWELL PARK CANCER INST
ELM AND CARLTON STREETS
BUFFALO, NY, 14263-6203

Domestic nonprofit research organization
Abstract
DESCRIPTION (provided by applicant): One of the major problems in the fight against cancer is the intrinsic or acquired resistance of tumors to current cancer treatments, particularly that associated with multidrug transporters (MDT; e.g. P-glycoprotein (P -gp) and the multidrug associated protein (MRP1)). The clinical failures of early P-gp inhibitors, which either caused non-specific toxicity or pharmacokinetic interactions with conventional chemotherapy agents, has significantly diminished the enthusiasm of pharmaceutical companies to develop MDT inhibitors. Nevertheless, drug resistance associated with these transporters is still a serious problem and the development of inhibitors against these proteins must be revisited using the knowledge and experience gained from previous failures to significantly increase the chances for success. The studies outlined in this proposal center around the optimization of Reversan, a MRP1 inhibitor that surpasses the activity of many known inhibitors of this MDT in the abs ence of toxicity. Our goal is to develop Reversan as an anti-cancer agent to be used together with standard chemotherapy to improve the efficacy of these conventional agents using liposomal formulations of Reversan or Reversan-drug combinations. Liposomal vehicles for in vivo delivery offer important features for tumor delivery of molecules, including decreased systemic clearance rates, decreased systemic toxicity as a result of decreased uptake of formulated agents by normal tissues and at the same time im proved efficacy due to increased uptake of the formulated agents by tumors. The data generated under this proposal will form the basis for the rational design of studies involving other conventional agents as well as for clinical trials using Reversan comb inations to assess the potential of Reversan as an anti-cancer agent. The significance of this project lies in its potential for identifying new treatment strategies for drug refractory cancers, such as neuroblastoma, that are currently faced with limited treatment options due to inherent and acquired drug resistance caused by MRP1 or MDTs in general. PUBLIC HEALTH RELEVANCE: One of the major problems in the fight against cancer is resistance to current cancer treatments, particularly resistance caused by m ultidrug transporters that pump standard cancer drugs out of cancer cells. Inhibitors of these transporters, such as Reversan-the focus of this proposal, when used together with standard chemotherapy should greatly increase the killing of tumor cells by al lowing the drugs to stay in tumor cells. Thus, Reversan has the potential to improve the clinical outcome for patients with limited treatment options due to multidrug resistance.

* information listed above is at the time of submission.

Agency Micro-sites

US Flag An Official Website of the United States Government