Clin Cancer Res 2002, 8: 221–232.PubMed 19. Browder T, Butterfield CE, Kraling BM, Shi B, Marshall B, O’Reilly MS, Folkman J: Antiangiogenic AZD3965 scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 2000, 60: 1878–1886.PubMed 20. Shaked Y, Bocci G, Munoz R, Man S, Ebos

JM, Hicklin DJ, Bertolini F, D’Amato R, Kerbel RS: Cellular and molecular surrogate markers to monitor targeted and non-targeted antiangiogenic drug activity and determine optimal biologic dose. Curr Cancer Drug Targets 2005, 5: 551–559.CrossRefPubMed 21. Morioka H, Weissbach L, Vogel T, Nielsen GP, Faircloth GT, Shao L, Hornicek FJ: Antiangiogenesis treatment combined with chemotherapy produces chondrosarcoma necrosis. Clin Cancer Res 2003, 9: 1211–1217.PubMed 22. Holtz DO, Krafty RT, Mohamed-Hadley A, Zhang L, Alagkiozidis I, Leiby B, Guo W, Gimotty PA, Coukos G: Should tumor VEGF expression influence decisions on combining low-dose chemotherapy with antiangiogenic

Raf inhibitor therapy? Preclinical modeling in ovarian cancer. J high throughput screening assay Transl Med 2008, 6: 2.CrossRefPubMed Competing interests The authors declare that they have no competing interests. Authors’ contributions RZB performed designed the project, cell culture, animal experiments and histologic analysis and drafted the manuscript. YW and QL prepared the recombinant human endostatin adenovirus and assisted with animal experiments. KX also contributed to animal

experiments. YQW supervised experimental work and revised the manuscript. LY, YSW and KL helped to construct and produce the recombinant adenovirus. YL and JMS assisted with histologic analysis. BH participated in research design. JYL performed the statistical analysis. QL helped to draft the manuscript. NT and ZWZ carried out cell culture. All authors read and approved the final manuscript.”
“Background Renal cell carcinoma (RCC) is the most common cancer of the kidney [1]. An estimated 16,000 new cases of RCC were diagnosed in Russian Federation in 2005. Up to 30% of patients with RCC present with metastatic disease every year, and recurrence develops in approximately 40% of patients treated for localized tumor [2]. High-dose interleukin-2 therapy rarely induces a durable complete response, and interferon alpha provides only pentoxifylline a modest survival advantage. Overall response rate with these cytokines is low (5 to 20%) [3]. A growing understanding of the underlying biology of RCC has led to development of vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib and sorafenib [4, 5]. The promising data with VEGF inhibition in metastatic RCC have established new opportunities for improving outcomes in this historically resistant malignancy. Combination of targeted therapy and biological agents has promising results. However, several questions remain unanswered concerning their optimal use.