A decade of tyrosine kinases: from gene discovery to therapeutics

Tyrosine kinases are key regulators of breast cancer cell survival and proliferation. Ten years ago, we conducted a screen for protein kinases expressed in primary human breast tumors and cultured cancer cells. Here, we review the progress from the last ten years in understanding the functions of these kinases with a focus on breast cancer. Three themes emerge: (1) tyrosine kinases regulate proliferation through the MAP Kinase pathway, (2) tyrosine kinases regulate cellular survival through the PI3 Kinase-Akt pathway, and (3) the cell cycle is regulated through a complex series of serine-threonine kinases. Our improved understanding of these signaling cascades has led to novel strategies for therapeutic intervention in breast cancer. (C) 2003 Elsevier Science Ltd. All rights reserved.