# USE OF MTAASE DEFICIENCY IN CANCER TREATMENT

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 1989 · $116,251

## Abstract

The goal is to develop a rationale for clinical trials in which
patients whose cancer cells are methylthioadenosine (MTA)
phosphorylase-deficient can be treated with a non-toxic regimen
consisting of methionine deprivation and MTA supplementation.
The specific aims are 1) to screen 200-300 human cancers for
MTA phosphorylase (MTAse) activity to determine the frequency
of MTAase deficiency in various tumor types, 2) to determine
the ability of methionine deprivation and MTA supplementation
to selectively inhibit MTAase-deficient malignant cells in vivo
in mice and 3) to determine the hematopoietic toxicity (if any)
of this regimen in vivo.  MTA is a naturally occurring
nucleoside which is degraded to methylthioribose-1-phosphate
(MTR-1-P) and adenine by MTA phosphorylase in all normal
mammalian cells.  Both of these products of MTAase action are
recycled:  adenine via the purine salvage pathway to the
nucleotide pool and MTR-1-P via Alpha-ketomethyl-thiobutyrate
to methionine.  Thus, in MTAase-containing (MTAase+) but not
MTAase-deficient (MTAase-) cells, supplemental MTA could
theoretically be utilized as a source of methionine and
adenine.  In fact, in vitro work has shown that MTAase+ cells
are able to proliferate normally in methionine-free medium if
supplemental MTA is added to the cultures.  In contrast,
MTAase- cells will not proliferate in methionine-free medium
when MTA is added.  Moreover, in vivo studies indicate that MTA
added to a methionine-free diet prevents the development of
methionine deficiency in mice.  In light of these observations
and the recent demonstration that a proportion of human acute
leukemias and solid tumors lack MTAase, it follows that some
human malignancies may be treatable with a regimen of
methionine starvation and MTA supplementation.

## Key facts

- **NIH application ID:** 3175797
- **Project number:** 5R01CA037881-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **SAM.gov UEI:** NPSNT86JKN51
- **Principal Investigator:** JOHN H FITCHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $116,251
- **Award type:** 5
- **Project period:** 1986-09-30 → 1990-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175797

## Citation

> US National Institutes of Health, RePORTER application 3175797, USE OF MTAASE DEFICIENCY IN CANCER TREATMENT (5R01CA037881-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175797. Licensed CC0.

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