# MECHANISM OF ACTION OF ANTITUMOR DRUGS

> **NIH NIH R01** · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · 1993 · $197,427

## Abstract

Our long term objectives are to understand the mechanisms of action of
topoisomerase-targeting antitumor drugs and to develop more effective
antitumor drugs for cancer chemotherapy.  In the past funding periods, we
and others have established that both human DNA topoisomerase I and
topoisomerase II are important antitumor drug targets.  Their mechanisms
of action have also been partially elucidated.  More recently, some
topoisomerase drugs have been shown to overcome MDR1-mediated resistance
and to exhibit strong antitumor activity against many refractory human
solid tumor xenografts in nude mice.  To further understand the
mechanisms of action of topoisomerase-targeting drugs and to develop more
effective antitumor drugs for cancer chemotherapy, we plan to: (1)
investigate the mechanism of action of DNA minor groove binding drugs
which we have recently shown to be a new class of topoisomerase
I-targeting drugs; (2) investigate the mechanism(s) of action
naphthoquinones and quinolones which may represent a new class(es) of
topoisomerase II-targeting drugs.  The roles of both 170 kDa and 180 kDa
isoforms of human DNA topoisomerase II in drug action will also be
studied. (3) investigate the roles of topoisomerases in genome
rearrangements using specific topoisomerase-targeting antitumor drugs.
(4) investigate the mechanism of drug specificity of human MDR1 and to
overcome MDR1-mediated resistance using topoisomerase-targeting antitumor
drugs.

## Key facts

- **NIH application ID:** 3178937
- **Project number:** 2R01CA039662-10
- **Recipient organization:** UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
- **Principal Investigator:** LEROY F LIU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $197,427
- **Award type:** 2
- **Project period:** 1985-04-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178937

## Citation

> US National Institutes of Health, RePORTER application 3178937, MECHANISM OF ACTION OF ANTITUMOR DRUGS (2R01CA039662-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178937. Licensed CC0.

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