# SENSITIZERS PLUS COMBINED MODALITIES IN LUNG TUMORS

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 1991 · $175,469

## Abstract

The major goal of this research program continues to be the
laboratory examination of treatment strategies aimed at
eradicating tumor cells growing in the lung.  This proposal will
investigate the role of extrinsic and intrinsic cellular factors and
their interplay in determining the response of lung cancer cells to
radiation, chemotherapeutic agents and nitroheterocyclic
sensitizers used alone or in combination.  Factors to be evaluated
for their effect on treatment response include cellular thiol levels
and potentially lethal damage repair (PLDR) capacity (intrinsic)
as well as alterations in the environment (extrinsic).  Experiments
using human lung cancer models will evaluate means of
manipulating these factors and assess whether such manipulations
can yield a therapeutic gain.  Emphasis will be placed on
determining the role of PLDR in the response on lung tumor cells
to radiation or chemotherapeutic agents.  This will be done in cell
lines grown both in tissue culture and as human tumor xenografts.
Comparing the in vitro and in vivo PLDR capacity will allow the
determination of the relevance of this factor in lung tumor
therapy response and could have important implications on how
best to attempt to predict clinical therapy outcome from
laboratory investigations.  Since cellular thiol concentrations can
affect the efficacy of a variety of anticancer agents, it is also an
objective to establish the importance of glutathione (GSH) levels
as determinants of lung tumor cell response to radiation and/or
drugs.  These studies will not only determine the relationship
between intrinsic GSH levels and therapeutic response but also
will assess the role of GSH recovery in this process.  Experiments
aimed at manipulating the treatment response through the
administration of the thiol depletor buthionine sulfoximine (BSO)
also will be carried out.  In particular, we will examine whether
the use of BSO to affect GSH metabolism will lead to more
effective potentiation of chemotherapeutic agents by hypoxic cell
sensitizers or more efficacious drug-radiation interactions.  The
potential therapeutic benefit which may be achieved through
these treatment strategies will be determined by also measuring
effects in critical normal tissues (lung and bone marrow).  These
investigations should yield information which will improve our
understanding of factors influencing cellular therapeutic response
and may guide the efforts for the most effective use of combined
modality therapies in lung cancer treatment.

## Key facts

- **NIH application ID:** 3176753
- **Project number:** 5R01CA038637-07
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **SAM.gov UEI:** F27KDXZMF9Y8
- **Principal Investigator:** DIETMAR W SIEMANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $175,469
- **Award type:** 5
- **Project period:** 1985-01-01 → 1992-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176753

## Citation

> US National Institutes of Health, RePORTER application 3176753, SENSITIZERS PLUS COMBINED MODALITIES IN LUNG TUMORS (5R01CA038637-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176753. Licensed CC0.

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