# CHEMODIFFERENTIATION AS AN APPROACH TO CANCER THERAPY

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE · 1987 · $238,993

## Abstract

It is the aim of the proposed study to examine the therapeutic potential
that attaches to the observed ability of clinically active anticancer
agents and of cell-derived factors to induce the in vitro differentiation
of various tumor cell lines.  Because this process is initiated at drug
concentrations that are minimally or noncytotoxic, greater selectivity may
be achievable than is possible with currently used maximally tolerated drug
doses.  This concept will be evaluated in vivo, using two murine myeloid
leukemia cell lines, M1 and RF/UM which, respectively, proliferate i.p. and
systemically, and are sensitive to treatment with anticancer agents.  Drug
and factor concentrations that are minimally or non-toxic to the host will
be employed and treatment schedules are to be devised capable of providing
maximal differentiation induction.  Parallel studies are to be carried out
in vitro to determine whether drug treatment renders leukemic cells
sensitive to differentiation induction by natural factors and whether such
treatment affects factor production itself.  Mechanistic studies are
projected, aimed at elucidating the molecular basis of drug- and factor-
induced differentiation.  Since the transition from proliferation to
differentiation occurs within hours after treatment, the early changes in
cellular protein and mRNA patterns that accompany this transition are to be
determined by two-dimensional gel electrophoresis of the radiolabelled
macromolecules.  Because drug-induced differentiation occurs after
inhibition of DNA synthesis and/or function, the nature of
differentiation-associated gene expression is to be assessed by determining
whether it involves new transcription or translation of pre-existing mRNA.
In contrast, tetradecanoylphorbol ester and natural differentiation factors
induce maturation without inhibiting DNA synthesis, and their effect
appears mediated via membrane-associated events.  These will be examined by
determining the modification of membrane proteins the agents bring about.
This experimental approach is expected to provide a meaningful assessment
of the role differentiation might play in cancer therapy.

## Key facts

- **NIH application ID:** 3173755
- **Project number:** 5R01CA036241-04
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE
- **Principal Investigator:** ALEXANDER BLOCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $238,993
- **Award type:** 5
- **Project period:** 1984-06-01 → 1988-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173755

## Citation

> US National Institutes of Health, RePORTER application 3173755, CHEMODIFFERENTIATION AS AN APPROACH TO CANCER THERAPY (5R01CA036241-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173755. Licensed CC0.

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