# CHEMODIFFERENTIATION AS AN APPROACH TO CANCER THERAPY

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE · 1991 · $138,427

## Abstract

Tumor cells are characterized by their arrest at stages of incomplete
maturation with retention of their capacity for sustained growth.
Therefore, approaches leading to the initiation of their differentiation
hold promise for use in cancer therapy.  To identify such approaches.
studies are proposed dealing with the mechanisms by which growth- and
differentiation signals control the proliferation and maturation of ML-1
human myeloblastic leukemia cells.  Our recent findings have shown that
two stages -competence and progression- are involved in the
differentiation process, the former stage being controlled by the
cytokines TNF-alpha and TGF-beta, the latter by transferrin, isolated
from leukocyte-conditioned medium and identified by sequencing.  The
mechanisms by which these two phases are activated and the relationship
they bear to the parallel phases activated by growth factors is to be
studied by 1) examining the effects differentiation-specific competence
factors exert on the expression and the extent of phosphorylation of the
receptor for the differentiation-progression factor transferrin; 2)
determining the effect the differentiation-specific competence and
progression signals exert on the expression of diverse proto-oncogenes
generally considered to be involved in the control of cell proliferation;
3) exploring the ability of differentiation-determining competence and
progression factors to bring about the therapeutic reduction of ML-1
leukemic cell populations when applied alone or in combination with
DNA-specific drugs, which render the cells sensitive to differentiation;
4) measuring the binding characteristics of the ML-1 growth-stimulating
and differentiation-inducing competence factors; 5) assaying the
reciprocal, concentration-dependent effects ML-1 growth- and
differentiation factors exert on each others' signals and 6) determining
the nature of the phospholipases targeted, the phosphoinositide
metabolites generated and the PKC subspecies activated by growth- as
compared to differentiation-inducing factors.

## Key facts

- **NIH application ID:** 3173751
- **Project number:** 2R01CA036241-08
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE
- **Principal Investigator:** ALEXANDER BLOCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $138,427
- **Award type:** 2
- **Project period:** 1984-06-01 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173751

## Citation

> US National Institutes of Health, RePORTER application 3173751, CHEMODIFFERENTIATION AS AN APPROACH TO CANCER THERAPY (2R01CA036241-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173751. Licensed CC0.

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