‘Accidental’ anti-angiogenic drugs: anti-oncogene directed signal transduction inhibitors and conventional chemotherapeutic agents as examples

摘要: A number of drugs currently being tested in clinical trials as possible angiogenesis inhibitors were not originally developed with the intention suppressing tumour angiogenesis. Thalidomide and interferon alpha are obvious examples such drugs. This list ‘accidental’ may include established agents conventional cytotoxic chemotherapeutic well new generation anticancer known anti-oncoprotein signal transduction inhibitors. With respect to former, potential inhibit could be result their ability cause collateral damaging eAects on cycling endothelial cells found newly formed blood vessels, or inhibiting other vital cell functions necessary for The antitumour vascular side-eAects chemotherapy optimised by administering continuously a more frequent (e.g. weekly even daily) basis at levels below maximum tolerated dose (MTD), especially when this is done combination anti-angiogenic growth factor (VEGF) receptor blocking antibodies. strategy minimise delay problems host toxicity acquired drug resistance. possibility mediated ras farnesyltransferase (ras FTI’s), which block tyrosine kinases ErbB2/neu) Herceptin, consequence oncogenes inducing upregulating various pro-angiogenic molecules VEGF (vascular factor) cells. Hence, treatment can lead downregulation cell-associated expression contribute an eAect vivo. In addition, some these also aAect certain ‘activated’ directly so An awareness experimental through blockade suppression has implications how used clinically, either alone, optimally treat cancer. # 2000 Elsevier Science Ltd. All rights reserved.