# ANTIESTROGEN/5-FU DRUG COMBINATIONS IN BREAST CANCER

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1988 · $118,368

## Abstract

Tamoxifen (TAM and 5-fluorouracil (FUra) are each commonly
used agents in the treatment of breast cancer.  However, they are
not routinely used in vivo in such a manner that exploits their
potential for synergistic interaction.  This project produced the
earliest published reports showing that TAM and FUra could be
combined in vitro against human breast cancer cells to produce
synergistic cytotoxicity.  Studies have since focused on the
mechanisms underlying this interaction, and the potential scope of
its application.  New drug-hormone combinations found to have
synergistic antiproliferative activity include TAM followed by
estradiol (E2) + sequenced MTX/FUra, and TAM + recombinant
alpha-interferon (alpha IFN).  Other drugs and mitogenic growth
factors will be studied in combination with TAM, E2, and FUra
looking for common biochemical mechanisms that might be
associated with synergistic chemoendocrine interactions.  These
assays will use cultured T47-D and MCF-7 cells, as well as MCF-7
clonal variants including the TAM resistant R27 cells and five
oncogene transfected subclones which over-express c-myc and are
less sensitive to TAM.  The project will continue to investigate
RNA- and estrogen receptor (ER)- mediated interactions between
TAM and FUra.  ER from control and drug treated cells will be
extracted looking for differences in binding affinity (kd),
sedimentation (S) and isoelectric point (pI), monoclonal antibody
idiotype specificity, and dependence on protease, phosphatase,
and RNase inhibitors.  Purified RNA from control and treated
cells will be probed for expression of oncogenes (c-myc, c-fos, c-
ras) and small regulatory sequences of RNA (U1, U3, 7Sk, 7SL).
These studies will hopefully provide new direction for
advancements in the treatment of breast cancer.

## Key facts

- **NIH application ID:** 3174336
- **Project number:** 5R01CA036773-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** Christopher Benz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $118,368
- **Award type:** 5
- **Project period:** 1983-08-15 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174336

## Citation

> US National Institutes of Health, RePORTER application 3174336, ANTIESTROGEN/5-FU DRUG COMBINATIONS IN BREAST CANCER (5R01CA036773-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174336. Licensed CC0.

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