PMID: 11916224Mar 28, 2002Paper

Prospects for combining hormonal and nonhormonal growth factor inhibition

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Alan WakelingJ M Gee

Abstract

In patients with estrogen receptor (ER)-negative disease or ER+ hormone-resistant disease, the dominant influence on tumor cell growth is growth factors, e.g., epidermal growth factor (EGF), heregulins, and insulin-like growth factors acting through specific receptor tyrosine kinases at the cell surface. This superfamily of ligand-activated growth factor receptors triggers cascades of biochemical signals that influence tumor cell motility, invasiveness, angiogenesis, and survival, as well as proliferation. In breast tumors, expression of epidermal growth factor receptor (EGFR) and/or erbB2 is associated with poor prognosis; the therapeutic utility of blocking these receptors has been established using trastuzumab (Herceptin), a monoclonal antibody that blocks erbB2 signaling. An alternative therapeutic approach is offered by small molecule inhibitors of EGFR-TK, exemplified by ZD1839 (Iressa), a potent and selective EGFR-TK inhibitor. Resistance to tamoxifen is associated with up-regulation of the EGFR-TK pathway and mitogen-activated protein kinase activity is substantially increased in tamoxifen-resistant MCF-7 cells. ZD1839 treatment of tamoxifen-resistant MCF-7 cells blocks mitogen-activated protein kinase activity. Further...Continue Reading

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