Researchers from Sunnybrook Health Science Center provide details of new studies and findings in the area of life sciences
2007 NOV 19 -- A new study, 'Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy,' is now available. "Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes," scientists in Toronto, Canada report. "However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered protein expression was found in a broad variety of tissues, and dose-dependent elevations were observed of several plasma proteins previously unassociated with this class of inhibitor, including G-CSF, SDF-1alpha, SCF, and osteopontin. Our results suggest that observed sunitinib-induced molecular plasma changes, including those both directly and indirectly targeted by drug, represent a systemic tumor-independent response to therapy and may correlate with the most efficacious antitumor doses, potentially having utility for defining the optimal biologic dose range for this drug class but not as predictive markers of tumor response or clinical benefit," wrote J.M. Ebos and colleagues, Sunnybrook Health Science Center. The researchers concluded: "They may also be relevant to drug-associated toxicities, drug resistance, and observed rapid tumor (re)growth seen after cessation of therapy." Ebos and colleagues published their study in Proceedings of the National Academy of Sciences of the United States of America (Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proceedings of the National Academy of Sciences of the United States of America, 2007;104(43):17069-74). For more information, contact J.M. Ebos, Sunnybrook Health Sciences Centre, Molecular and Cellular Biology Research, 2075 Bayview Avenue, Toronto, Ontario, Canada. Publisher contact information for the journal Proceedings of the National Academy of Sciences of the United States of America is: National Acad Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA. Keywords: Canada, Toronto, Life Sciences, Vascular Endothelial Growth Factor, Therapy, Treatment, Small Molecule Inhibitor, Pharmaceuticals. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
|
