# MULTIDRUG RESISTANCE AND P-GLYCOPROTEIN IN HUMAN CANCER

> **NIH NIH R01** · ONTARIO CANCER INSTITUTE · 1991 · $125,326

## Abstract

The goal of this application contains two parts.  The first is to determine
if the development of P-glycoprotein associated multidrug resistance (MDR)
affect the clinical response of a patient to cancer chemotherapy.  The
second part is to investigate mechanisms regulating P-glycoprotein
expression in normal and malignant cells.  In model systems, P-glycoprotein
has been shown to be causative of MDR and is thought to function as an
energy-dependent drug efflux pump.  Although other mechanisms of MDR have
been proposed, the P-glycoprotein-mediated form is the best documented and
appears to have clinical relevance.

Since P-glycoprotein expression appears to be a reliable molecular marker
for the MDR phenotype, one specific aim is to develop sensitive and
specific reagents for the immunohistochemical localization of P-
glycoprotein in tumor biopsy samples.  One approach which has met with
success is to map the epitopes of P-glycoprotein monoclonal antibodies and
to use synthetic competing peptides to define epitope-specific staining.
This approach will be extended to a number of P-glycoprotein monoclonal
antibodies.  Such reagents will be used for correlating P-glycoprotein
expression and clinical response.

The second specific aim is to determine if chemosensitizing agents
azidopine and cyclosporin A interact with P-glycoprotein at a similar
domain.  Such knowledge will form the basis for a molecular understanding
of how such structurally different molecules are able to reverse the MDR
phenotype.

The third specific aim is to study the mechanisms of increased P-
glycoprotein expression in tumor cell lines.  We particularly wish to
investigate the observation that a significant proportion of patients
present with P-glycoprotein positive tumors even prior to chemotherapy.
This may provide insights into why some tumors are not responsive to
chemotherapy from the outset.

We believe that accomplishment of the specific aims described in this
application will add significantly to our knowledge of malignant
development and therapeutic efficacy in human cancer.

## Key facts

- **NIH application ID:** 3174834
- **Project number:** 5R01CA037130-08
- **Recipient organization:** ONTARIO CANCER INSTITUTE
- **Principal Investigator:** VICTOR LING
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $125,326
- **Award type:** 5
- **Project period:** 1990-07-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174834

## Citation

> US National Institutes of Health, RePORTER application 3174834, MULTIDRUG RESISTANCE AND P-GLYCOPROTEIN IN HUMAN CANCER (5R01CA037130-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174834. Licensed CC0.

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