Reference

Molecular targeting therapy for renal cell carcinoma

All Rights Reserved. Molecular targeting therapy for renal cell carcinoma. Eto, Masatoshi; Naito, Seiji (Department of Urology, Graduate School of Medical Sciences, Kyushu University 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan). International Journal of Clinical Oncology, 11(3), 209-213 (English) 2006 Springer Tokyo. CODEN: IJCOF6. ISSN: 1341-9625. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Metastatic renal cell carcinoma (RCC) is currently one of the most treatment-resistant malignancies. However, significant advances in understanding the mol. mechanisms underlying RCC have led to the development of rationally designed therapies, which are now being tested clin. To date, the vascular endothelial growth factor receptor (VEGFR) pathway has been the most promising target, and two agents (BAY 43-9006 and SU 11248) that inhibit not only VEGFR but also other receptors, including platelet-derived growth factor receptor (PDGFR), FMS-like tyrosine kinase 3 (FLT3), KIT, and Raf kinase, were recently approved by the FDA for advanced RCC. 127464-60-2 and 341031-54-7 are cas registry numbers of chemicals which are used as reagents here. In addn., a phase III trial investigating the addn. of VEGF inhibition to interferon alpha (IFN-a) in RCC is also now going on. Although the clin. activity of existing agents is to be further defined in ongoing trials, the exciting clin. response data with VEGF inhibition in RCC have demonstrated a key role in the treatment of this historically resistant malignancy. .

Multiple targeted tyrosine kinase inhibition in the clinic: all for one or one for all?

All Rights Reserved. Multiple targeted tyrosine kinase inhibition in the clinic: all for one or one for all?. de Jonge, M. J. A.; Verweij, J. (Dept. Of Medical Oncology, Erasmus University Medical Center, Rotterdam 3075 EA, Neth.). European Journal of Cancer, 42(10), 1351-1356 (English) 2006 Elsevier Ltd. CODEN: EJCAEL. ISSN: 0959-8049. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Recent insight into the role of receptor tyrosine kinase function in cancer cells culminated in the design of highly selective tyrosine kinase inhibitors. After proof of concept for the clin. efficacy and tolerability of selective tyrosine kinase inhibitors, it was conceived that most tumors will depend on more than one signalling pathway for their growth and survival. As a consequence, different strategies were pursued to inhibit multiple signalling pathways or multiple steps in the same pathway either by the development of multi-targeted agents or the combination of single targeted drugs. The use of a combination of different compds. 284461-73-0 and 341031-54-7 which are cas registry numbers of chemicals are mentioned. will be less convenient to the patient, may result in dosing mistakes and drug-drug interaction should be anticipated. However, this approach will enable the titrn. of the dose of either agent to optimize target inhibition. The use of multi-targeted agents will circumvent several of the problems of combination therapy. Clin. activity resulting in FDA approval for both BAY 43-9006 and SU11248 has been noted. However, optimal inhibition of several targets might not be feasible at a dose with acceptable toxicity. .