GROWTH REGULATION AS TARGETS IN BREAST CANCER TREATMENT

  • Lippman, Marc E, (PI)
  • Sausville, Edward (PI)
  • Martin, Mary Beth (PI)
  • Dickson, Robert B. (PI)
  • Wellstein, Anton (PI)
  • Clark, Robert (PI)

Project: Research project

Description

Breast cancer is overwhelmingly the most common malignancy of women.
Despite substantial efforts, incidence rates and mortality rates have not
changed significantly. New therapeutic approaches are clearly needed. Our
goals are to develop new treatment strategies for human breast cancer which
are derived from an in depth analysis of cellular and molecular events that
control mitogenesis and malignant progression. Specifically, a variety of
critical steps involved in the breast cancer process will be examined in
detail. In program one information on regulation of gene expression by
estrogens as well as regulation of expression of steroid and polypeptide
receptors for growth factors will be investigated. Specific focus will be
paid to the retinoblastoma gene and its role in breast cancer progression.
A series of approaches aimed at interrupting signal transduction pathways
that lie between ligand binding to cell surface receptor and specific
phenotypic effects leading to malignant progression will be the subject of
program area two. In program area three, a series of models which mimic the
progression of human breast cancer from the hormone dependent phenotype to
hormone unresponsiveness will be further explored along with several
approaches geared towards blocking this progression. We have substantial
preliminary information that suggests that heparin binding growth factors
play an important role in epithelial transformation of human breast cancer.
We have designed several strategies to interrupt the activity of these
growth factors and their exploitation as antitumor therapies will be
explored in program area four. Finally, in program area five we will study
the control of invasiveness of breast cancer modulated through cell surface
proteases. A series of strategies designed to further understand the
cellular and molecular biology of these critical regulators of the
metastatic phenotype as well as several approaches to their inhibition will
be developed as potential antimetastatic therapies.
StatusFinished
Effective start/end date5/21/904/30/95

Funding

  • National Institutes of Health: $633,489.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $694,736.00
  • National Institutes of Health: $655,095.00

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Breast Neoplasms
Growth
Therapeutics
Retinoblastoma Genes
Phenotype
Gene Expression Regulation
Cell Surface Receptors
Heparin
Molecular Biology
Signal Transduction
Intercellular Signaling Peptides and Proteins
Steroids
Hormones
Ligands
Mortality
Incidence
Neoplasms

ASJC

  • Medicine(all)