# SIMULATED TUMOR THERAPY WITH AN IN VITRO MODEL

> **NIH NIH R01** · BRITISH COLUMBIA CANCER AGENCY · 1990 · $111,193

## Abstract

Most human malignancies will respond to current
chemotherapeutic treatment regimens, yet few neoplasms can be
cured by chemotherapy alone.  Development of more effective
drugs is thus necessary, but we believe that a high priority should
also be placed on optimizing the use of available agents, which in
turn requires a better understanding of the factors which
modulate drug activity in a tumor.  While drug 'resistance' is
generally implicated as the cause of treatment failure, it is
seldom possible to know when, where, or why resistant cells
appear in the tumor mass.  This information can, however, be
determined in certain laboratory models, like V79 multicell
spheroids in tissue culture.  We thus intend to evaluate several
clinically-used chemotherapeutic agents in spheroids, emphasizing
regional and temporal variations in cytotoxicity; our results will
suggest ways to use each agent more effectively, and provide
additional criteria for selecting (and using) drug combinations.

Regional variations in drug efficacy will be studied in spheroids
stained with slowly-penetrating, non-toxic fluorescent dyes.
Since the dyes are retained in disaggregated cells, a fluorescence-
activated cell sorter can be used to select subpopulations with
specified stain intensities; the clonogenicity of these sorted cells
then defines the drug toxicity throughout the spheroid.  The
location, timing and degree of resistance to each drug will suggest
useful combinations, as well as indicating ways to improve single-
agent efficacy.  In subsequent multidrug studies, therapeutically
useful interactions, including differential (complementary)
toxicity, reoxygenation, cell cycle perturbations, metabolic
alterations, and/or direct interaction of lesions, will be identified
and quantified.  The resulting information will supplement that
already available for these clinically effective drugs, so promising
combinations, doses and sequences and can be evaluated in
patients without delay.

## Key facts

- **NIH application ID:** 3175587
- **Project number:** 5R01CA037775-06
- **Recipient organization:** BRITISH COLUMBIA CANCER AGENCY
- **SAM.gov UEI:** LKF9B2BABMM6
- **Principal Investigator:** RALPH E. DURAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $111,193
- **Award type:** 5
- **Project period:** 1984-07-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175587

## Citation

> US National Institutes of Health, RePORTER application 3175587, SIMULATED TUMOR THERAPY WITH AN IN VITRO MODEL (5R01CA037775-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175587. Licensed CC0.

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