# MECHANISM(S) OF TUMOR PROGRESSION AND METASTASIS

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1987 · $116,165

## Abstract

The primary goal of this proposal is to define (at least in part) the
mechanism(s) of tumor progression.  To achieve this, we plan to
further analyse the role of DNA hypomethylation in the
progression of tumors from the benign to the malignant state.
Because it is possible that hypomethylation in itself may be
insufficient to achieve this transition (i.e., secondary agents likely
play a role), the central focus of this proposal is to study the role
of genomic destabilization in tumor progression.  We believe that
agents such as 5-aza-d-Cyd and DFMO, which respectively cause
DNA hypomethylation and polyamine depletion, can broadly
destabilize DNA and result in augmented genomic injury induced
by secondary agents.  The agents which we have chosen to provide
'secondary' injury are MNNG (a monofunctional alkylating agent)
and m-AMSA, an intercalating agent.  The key factor in these
studies is that the effects of each of these agents, 5-aza-d-Cyd,
DFMO, MNNG and m-AMSA, can be quantitated biochemically.
In addition, we have chosen to study tumor cell lines with known
characteristics so that specific phenotypic changes induced by
each agent alone or in defined combinations can be readily
assessed.  Four phenotypic characteristics will be analyzed
including the generation of drug resistant mutants, metastatic
variants, immunogenic variants, and changes in isozymes.
Chromosomal rearrangements will also be assessed.  These
protocols will therefore allow for a systematic analysis (using the
parameters outlined) of the role of genomic instability in the
generation of phenotypic diversity.

A secondary goal of these studies is to address the role of DNA
hypomethylation in carcinogenesis.  Both an in vivo and in vitro
model for potential murine lymphoma/leukemia generation are
outlined.

## Key facts

- **NIH application ID:** 3179223
- **Project number:** 5R01CA039853-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** PHILIP FROST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $116,165
- **Award type:** 5
- **Project period:** 1984-08-01 → 1989-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179223

## Citation

> US National Institutes of Health, RePORTER application 3179223, MECHANISM(S) OF TUMOR PROGRESSION AND METASTASIS (5R01CA039853-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179223. Licensed CC0.

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