Project 170762

Molecular and functional studies of ENT proteins: towards an understanding of their role in cancer therapeutics.

170762

Molecular and functional studies of ENT proteins: towards an understanding of their role in cancer therapeutics.

$751,305
Project Information
Study Type: Other Mechanistic_Study
Therapeutic Area: Oncology
Research Theme: Biomedical
Disease Area: cancer
Data Type: Canadian
Institution & Funding
Principal Investigator(s): Young, James D
Co-Investigator(s): Cass, Carol E
Institution: University of Alberta
CIHR Institute: Cancer Research
Program: Operating Grant
Peer Review Committee: Molecular & Cellular Biology of Cancer
Competition Year: 2008
Term: 5 yrs 0 mth
Abstract Summary

A number of nucleoside analogs have anticancer activities and are either in current clinical use or in various stages of preclinical evaluation. Since the pharmacological targets of nucleoside drugs are intracellular, penetration of cells by passage across plasma membranes and, subsequently, across intracellular membrane barriers are critical determinants of drug activities and host toxicities. We have achieved the molecular cloning and structural identification of human and rodent members of two new protein families involved in nucleoside transport across cell membranes: the equilibrative bidirectional (ENT) family and the concentrative sodium/nucleoside cotransporter (CNT) family. The research projects described in this application will study the relationships between molecular structure and the ability of ENT proteins to move molecules across plasma and intracellular membranes. The goal of this research is to increase our understanding of mechanisms by which cells utilize nucleosides and to use knowledge of these mechanisms to enhance the therapeutic selectivity of nucleoside drugs.

Research Characteristics

This project includes the following research characteristics:

Regulatory Pathway
Knowledge Translation Focus
Biomarker Endpoints
Personalized Medicine
Study Justification

"study the relationships between molecular structure and the ability of ENT proteins to move molecules across plasma and intracellular membranes"

Novelty Statement

"The goal of this research is to increase our understanding of mechanisms by which cells utilize nucleosides and to use knowledge of these mechanisms to enhance the therapeutic selectivity of nucleoside drugs."

Methodology Innovation

studying the molecular structure and function of ENT proteins to enhance the therapeutic selectivity of nucleoside drugs

Keywords
Cancer Therapeutics Membrane Protein Biochemistry Membrane Transporters Nucleoside Drugs Nucleoside Transport Recombinant Dna Technology