Hyder's overall aim is to identify hormone dependent molecular targets, and selective steroid receptor modulators, that can be utilized for anti-angiogenic therapy of endocrine dependent disease such as breast, uterine and prostate cancer.

Formation of new blood vessels, or angiogenesis, is crucial for normal processes such as embryonic development, wound healing, and endometrial regeneration following menstruation. Angiogenesis is also essential for tumor growth and metastasis. An emerging field in cancer therapeutics is the targeting of new blood vessels to curtail tumor growth. It has been known for a while that breast and uterine cancers are under the influence of female sex-steroid hormones (estrogen and progesterone), and that expansion of any tumor is dependent on the formation of new blood vessels.

Surprisingly, very little information is available on how steroid hormones regulate the process of angiogenesis in normal or neoplastic breast and uterine cells. Hyder's laboratory is currently focusing on the role of steroid hormones, clinically relevant anti-hormones, and endocrine-disruptors to understand the basic mechanisms involved in hormone driven angiogenesis in breast, and uterine tissue. Hyder's team has recently discovered that one of the most potent angiogenic growth factor, Vascular Endothelial Growth Factor (VEGF) is under hormonal control in the breast and uterine cells. Hyder is now determining the role of estrogen and progesterone receptors in VEGF induction at the cellular and molecular level by examining the interaction of receptors with the VEGF gene.

Another focus of Hyder'slaboratory is to investigate the molecular mechanisms of steroid hormone action with a current focus on the role of natural and synthetic ligands in modulating the biological activity of steroid receptors. Hyder's interest in this area stems from the fact that one ligand can have diverse biological effects in different target tissues. While ligands may function as agonists in one tissue, the same ligand may have an opposite effect in another tissue that contains the same steroid receptor. Many synthetic ligands (agonists/antagonists) are consumed by millions of women all over the world for oral contraception, hormone replacement therapy or treatment of breast cancer. Consumption of some of these ligands are associated with increased risk of breast and/or uterine abnormalities. Hyder is currently interested in the mechanisms of action of anti-hormones that have mixed agonist/antagonist properties (e.g tamoxifen; mifepristone), pure antagonists (Faslodex), and complicated antagonists that bind one type of steroid receptor, but influence the biological activity of other receptors by cross-talk mechanisms.

Hyder is examining if cross-talk mechanisms involve alternative pathways (e.g. MAP Kinase), resulting in non-ligand dependent activation/inhibition of certain receptors. He anticipates that understanding the molecular basis/pharmacology of anti-hormone-receptor interactions will allow development of better therapeutic modalities for treatment of hormone dependent tumors, as well as endometriosis, osteoporosis and infertility.

Role of Steroid Hormones in Breast Tumor Progression and Metastasis: Regulation of Angiogenic Growth Factors

Mechanisms of Steroid Hormone Action and Anti-Hormone Resistance

Novel Therapeutic Approaches for Anti-Angiogenic Therapy of Breast Cancer