# TUMOR/HOST HETEROGENEITY AS FACTORS IN DRUG RESPONSE

> **NIH NIH R01** · SOUTHERN RESEARCH INSTITUTE · 1987 · $137,666

## Abstract

A major problem in the chemotherapy of cancer in man is the
variation in response of a single histological type of malignancy to
a given drug.  It is also a well-established fact that individual
advanced transplanted tumors of similar size and histology exhibit
responses to a drug that range from minimal to complete
regression and cure.  That tumor-to-tumor variability in perfusion
and drug distribution was a major factor in the variable response
of mammary adenocarcinoma 16/C to melphalan was
demonstrated during the initial period of this grant.  The
distribution of two nitroimidazole radiation sensitizers was
uniform in the same tumors that exhibited limited and uneven
distribution of melphalan.  We propose to investigate the
distribution of other agents or classes of agents such as
mitomycin C, an antibiotic with unique pharmacological
properties, in tumor regions of low perfusion, as delineated by a
visible dye.  Prior or simultaneous treatment of tumor-bearing
mice with agents to modify the distribution of melphalan will be
investigated.  We plan to investigate the tumor-to-tumor
variability of perfusion and drug distribution in a second
histological type of murine tumor, the M5076 sarcoma, and the
A549 human lung adenocarcinoma as a xenograft in athymic mice.
We plan to seek a correlation between readily measurable clinical
chemistry and hematology parameters, the plasma levels of
melphalan following a standard dose, and concentrations of
melphalan in tumor regions of high and low perfusion.  Similar
correlations will be attempted in mice pretreated with melphalan
and in mice following dose adjustments to reduce toxicity.  We
further propose to investigate intracellular levels of melphalan in
tumor regions of high and low perfusion.  These studies have
immediate clinical significance for chemotherapy of tumors of
the same histologic type and exhibit variable responses to
effective chemotherapy and for rational dose adjustment.

## Key facts

- **NIH application ID:** 3174841
- **Project number:** 2R01CA037132-04
- **Recipient organization:** SOUTHERN RESEARCH INSTITUTE
- **SAM.gov UEI:** CDZJAJJHJMH5
- **Principal Investigator:** LINDA K SIMPSON-HERREN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $137,666
- **Award type:** 2
- **Project period:** 1984-05-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174841

## Citation

> US National Institutes of Health, RePORTER application 3174841, TUMOR/HOST HETEROGENEITY AS FACTORS IN DRUG RESPONSE (2R01CA037132-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174841. Licensed CC0.

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