# BASIC STUDIES OF EXPERIMENTAL TUMOR MODELS

> **NIH NIH R01** · SRI INTERNATIONAL · 1992 · $285,564

## Abstract

It is hypothesized that both intrinsic cellular properties and extrinsic
microenvironmental conditions in human tumors play significant direct and
indirect roles in determining basic tumor cellular characteristics which
influence sensitivity to therapeutic modalities such as ionizing
radiation.  Little is known about these heterogeneous intrinsic and
extrinsic properties of human tumor cells with respect to radiation
sensitivity because, for the most part, such studies await the development
of appropriate experimental models and techniques.  Methods and
experimental models need to be developed to characterize this
heterogeneity, to evaluate mechanisms affecting biological behavior and
responsiveness to therapy, to develop and evaluate new therapeutic
strategies, and to predict for therapeutic responsiveness.  The research
program proposed here includes experiments designed to compare the
usefulness and relevance for radiation therapy of multicell spheroids,
clonogenic stem cell assays, and xenografts.  The specific aims of the
experiments are (1) to optimize and characterize the growth in these 3
model systems of cell isolates from selected human cancer (mainly squamous
cell carcinoma), (2) to directly determine the influence of certain
specific external environmental conditions on intra-spheroid oxygenation
and on cellular heterogeneities, and (3) to use these in vitro and in vivo
model systems to determine the importance to the overall radiation response
of human tumors at different stages of growth of intrinsic cell
sensitivity, intercellular contact, repair, differentiation, hypoxia, and
altered growth kinetics such as the development of quiescent cell
populations.  The central general questions we are asking are (a) What are
the relative strengths and limitations of the 3 model systems for growing
and characterizing human cancer cells?  (b) Do human tumor cells under
experimental conditions in vitro reflect the important in vivo properties?
(c) What assays and endpoints are most informative for characterizing
clinically relevant biological behavior and for predicting therapeutic
responsiveness?  (d) What are some of the inter-patient tumor differences
responsible for sensitive and resistant disease?  (e) What therapeutic
strategies using radiation alone or combined with drugs would be effective
for resistant tumors?  The research proposed represents the initial phases
of a concentrated, collaborative effort to more directly study human cancer
in appropriate model systems which can evaluate the significance of the
dynamic nature of cellular and environmental diversity that occurs at
different stages of tumor growth.

## Key facts

- **NIH application ID:** 3175405
- **Project number:** 5R01CA037618-09
- **Recipient organization:** SRI INTERNATIONAL
- **SAM.gov UEI:** SRG2J1WS9X63
- **Principal Investigator:** ROBERT M SUTHERLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $285,564
- **Award type:** 5
- **Project period:** 1984-08-01 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175405

## Citation

> US National Institutes of Health, RePORTER application 3175405, BASIC STUDIES OF EXPERIMENTAL TUMOR MODELS (5R01CA037618-09). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3175405. Licensed CC0.

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