Antiangiogenic therapy: impact on invasion, disease progression, and metastasis
Tóm tắt
Từ khóa
Tài liệu tham khảo
US Department of Health and Human Services FDA US Food and Drug Administration [online] , (2011).
Abdollahi, A. & Folkman, J. Evading tumor evasion: current concepts and perspectives of anti-angiogenic cancer therapy. Drug Resist. Updat. 13, 16–28 (2010).
Bergers, G. & Hanahan, D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8, 592–603 (2008).
Ebos, J. M. et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15, 232–239 (2009).
Pàez-Ribes, M. et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15, 220–231 (2009).
Allegra, C. J. et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J. Clin. Oncol. 29, 11–16 (2011).
de Gramont, A. et al. AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer [abstract]. J. Clin. Oncol. 29 (Suppl. 4), a362 (2011).
Miles, D. et al. Disease course patterns after discontinuation of bevacizumab: pooled analysis of randomized phase III trials. J. Clin. Oncol. 29, 83–88 (2011).
Bagri, A., Kouros-Mehr, H., Leong, K. G. & Plowman, G. D. Use of anti-VEGF adjuvant therapy in cancer: challenges and rationale. Trends Mol. Med. 16, 122–132 (2010).
Heath, V. L. & Bicknell, R. Anticancer strategies involving the vasculature. Nat. Rev. Clin. Oncol. 6, 395–404 (2009).
Boere, I. A., Hamberg, P. & Sleijfer, S. It takes two to tango: combinations of conventional cytotoxics with compounds targeting the vascular endothelial growth factor-vascular endothelial growth factor receptor pathway in patients with solid malignancies. Cancer Sci. 101, 7–15 (2010).
Ivy, S. P., Wick, J. Y. & Kaufman, B. M. An overview of small-molecule inhibitors of VEGFR signaling. Nat. Rev. Clin. Oncol. 6, 569–579 (2009).
Saltz, L. B. et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J. Clin. Oncol. 26, 2013–2019 (2008).
Wilkerson, J. & Fojo, T. Progression-free survival is simply a measure of a drug's effect while administered and is not a surrogate for overall survival. Cancer J. 15, 379–385 (2009).
Wolter, P., Beuselinck, B., Pans, S. & Schöffski, P. Flare-up: an often unreported phenomenon nevertheless familiar to oncologists prescribing tyrosine kinase inhibitors. Acta Oncol. 48, 621–624 (2009).
Desar, I. M. et al. The reverse side of the victory: flare up of symptoms after discontinuation of sunitinib or sorafenib in renal cell cancer patients. A report of three cases. Acta Oncol. 48, 927–931 (2009).
Cacheux, W. et al. Reversible tumor growth acceleration following bevacizumab interruption in metastatic colorectal cancer patients scheduled for surgery. Ann. Oncol. 19, 1659–1661 (2008).
Stein, W. D., Yang, J., Bates, S. E. & Fojo, T. Bevacizumab reduces the growth rate constants of renal carcinomas: a novel algorithm suggests early discontinuation of bevacizumab resulted in a lack of survival advantage. Oncologist 13, 1055–1062 (2008).
Mancuso, M. R. et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J. Clin. Invest. 116, 2610–2621 (2006).
Levashova, Z. et al. Molecular imaging of changes in the prevalence of vascular endothelial growth factor receptor in sunitinib-treated murine mammary tumors. J. Nucl. Med. 51, 959–966 (2010).
Nagengast, W. B. et al. VEGF-PET imaging is a noninvasive biomarker showing differential changes in the tumor during sunitinib treatment. Cancer Res. 71, 143–153 (2011).
di Tomaso, E. et al. Glioblastoma recurrence after cediranib therapy in patients: lack of “rebound” revascularization as mode of escape. Cancer Res. 71, 19–28 (2011).
La Vine, D. B., Coleman, T. A., Davis, C. H., Carbonell, C. E. & Davis, W. B. Frequent dose interruptions are required for patients receiving oral kinase inhibitor therapy for advanced renal cell carcinoma. Am. J. Clin. Oncol. 33, 217–220 (2010).
Gore, M. E. et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 10, 757–763 (2009).
van der Veldt, A. A. et al. Predictive factors for severe toxicity of sunitinib in unselected patients with advanced renal cell cancer. Br. J. Cancer 99, 259–265 (2008).
Riechelmann, R. P. et al. Sorafenib for metastatic renal cancer: the Princess Margaret experience. Am. J. Clin. Oncol. 31, 182–187 (2008).
Yoo, C. et al. The efficacy and safety of sunitinib in Korean patients with advanced renal cell carcinoma: high incidence of toxicity leads to frequent dose reduction. Jpn. J. Clin. Oncol. 40, 980–985 (2010).
Johannsen, M. et al. Can tyrosine kinase inhibitors be discontinued in patients with metastatic renal cell carcinoma and a complete response to treatment? A multicentre, retrospective analysis. Eur. Urol. 55, 1430–1438 (2009).
Sablin, M. P. et al. Sequential sorafenib and sunitinib for renal cell carcinoma. J. Urol. 182, 29–34 (2009).
Dudek, A. Z., Zolnierek, J., Dham, A., Lindgren, B. R. & Szczylik, C. Sequential therapy with sorafenib and sunitinib in renal cell carcinoma. Cancer 115, 61–67 (2009).
Tamaskar, I. et al. Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy. J. Urol. 179, 81–86 (2008).
Hammers, H. J. et al. Reversible epithelial to mesenchymal transition and acquired resistance to sunitinib in patients with renal cell carcinoma: evidence from a xenograft study. Mol. Cancer Ther. 9, 1525–1535 (2010).
Ellis, L. M. & Haller, D. G. Bevacizumab beyond progression: does this make sense? J. Clin. Oncol. 26, 5313–5315 (2008).
Cohn, A. L. et al. Clinical outcomes in bevacizumab (BV)-treated patients (pts) with metastatic colorectal cancer (mCRC): Results from ARIES observational cohort study (OCS) and confirmation of BRiTE data on BV beyond progression (BBP) [abstract]. J. Clin. Oncol. 28 (Suppl.), a3596 (2010).
Burger, R. A. et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study [abstract]. J. Clin. Oncol. 28 (Suppl.), aLBA1 (2010).
Perren, T. et al. ICON7: A phase III Gynaecologic Cancer InterGroup (GCIG) trial of adding bevacizumab to standard chemotherapy in women with newly diagnosed epithelial ovarian, primary peritoneal or fallopian tube cancer [abstract]. Ann. Oncol. 21 (Suppl. 8), aLBA3 (2010).
Ebos, J. M., Lee, C. R. & Kerbel, R. S. Tumor and host-mediated pathways of resistance and disease progression in response to antiangiogenic therapy. Clin. Cancer Res. 15, 5020–5025 (2009).
Norden, A. D. et al. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 70, 779–787 (2008).
Narayana, A. et al. Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival. J. Neurosurg. 110, 173–180 (2009).
Fischer, I. et al. High-grade glioma before and after treatment with radiation and Avastin: initial observations. Neuro. Oncol. 10, 700–708 (2008).
Mathews, M. S., Linskey, M. E., Hasso, A. N. & Fruehauf, J. P. The effect of bevacizumab (Avastin) on neuroimaging of brain metastases. Surg. Neurol. 70, 649–652 (2008).
Zuniga, R. M. et al. Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J. Neurooncol. 91, 329–336 (2009).
Iwamoto, F. M. et al. Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology 73, 1200–1206 (2009).
Zuniga, R. M. et al. Rebound tumour progression after the cessation of bevacizumab therapy in patients with recurrent high-grade glioma. J. Neurooncol. 99, 237–242 (2010).
Verhoeff, J. J. et al. Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme. BMC Cancer 9, 444 (2009).
Narayana, A. et al. Bevacizumab in recurrent high-grade pediatric gliomas. Neuro. Oncol. 12, 985–990 (2010).
Narayana, A. et al. Change in pattern of relapse after antiangiogenic therapy in high-grade glioma. Int. J. Radiat. Oncol. Biol. Phys. doi: 10.1016/j.ijrobp.2010.10.038.
Rubenstein, J. L. et al. Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption. Neoplasia 2, 306–314 (2000).
Kunkel, P. et al. Inhibition of glioma angiogenesis and growth in vivo by systemic treatment with a monoclonal antibody against vascular endothelial growth factor receptor-2. Cancer Res. 61, 6624–6628 (2001).
Blouw, B. et al. The hypoxic response of tumors is dependent on their microenvironment. Cancer Cell 4, 133–146 (2003).
Verhoeff, J. J. et al. Tumour control by whole brain irradiation of anti-VEGF-treated mice bearing intracerebral glioma. Eur. J. Cancer 45, 3074–3080 (2009).
Lucio-Eterovic, A. K., Piao, Y. & de Groot, J. F. Mediators of glioblastoma resistance and invasion during antivascular endothelial growth factor therapy. Clin. Cancer Res. 15, 4589–4599 (2009).
Gomez-Manzano, C. et al. VEGF Trap induces antiglioma effect at different stages of disease. Neuro. Oncol. 10, 940–945 (2008).
de Groot, J. F. et al. Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice. Neuro. Oncol. 12, 233–242 (2010).
Lamszus, K. et al. Inhibition of glioblastoma angiogenesis and invasion by combined treatments directed against vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and vascular endothelial-cadherin. Clin. Cancer Res. 11, 4934–4940 (2005).
Leenders, W. P. et al. Antiangiogenic therapy of cerebral melanoma metastases results in sustained tumor progression via vessel co-option. Clin. Cancer Res. 10, 6222–6230 (2004).
Chamberlain, M. C. Radiographic patterns of relapse in glioblastoma. J. Neurooncol. 101, 319–323 (2011).
Petrelli, F., Cabiddu, M., Carpo, M., Ghilardi, M. & Barni, S. Progression of intramedullary metastasis during perioperative cessation of sunitinib. Nat. Rev. Urol. 7, 634–637 (2010).
Plimack, E. R., Tannir, N., Lin, E., Bekele, B. N. & Jonasch, E. Patterns of disease progression in metastatic renal cell carcinoma patients treated with antivascular agents and interferon: impact of therapy on recurrence patterns and outcome measures. Cancer 115, 1859–1866 (2009).
Crawford, Y. & Ferrara, N. Tumor and stromal pathways mediating refractoriness/resistance to anti-angiogenic therapies. Trends Pharmacol. Sci. 30, 624–630 (2009).
Nguyen, D. X., Bos, P. D. & Massagué, J. Metastasis: from dissemination to organ-specific colonization. Nat. Rev. Cancer 9, 274–284 (2009).
Paget, S. The distribution of secondary growths in cancer of the breast. Lancet 133, 571–573 (1889).
Hirota, K. & Semenza, G. L. Regulation of angiogenesis by hypoxia-inducible factor 1. Crit. Rev. Oncol. Hematol. 59, 15–26 (2006).
Yu, J. L., Rak, J. W., Coomber, B. L., Hicklin, D. J. & Kerbel, R. S. Effect of p53 status on tumor response to antiangiogenic therapy. Science 295, 1526–1528 (2002).
Rapisarda, A. & Melillo, G. Role of the hypoxic tumor microenvironment in the resistance to anti-angiogenic therapies. Drug Resist. Updat. 12, 74–80 (2009).
Pennacchietti, S. et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3, 347–361 (2003).
Bidard, F. C., Pierga, J. Y., Vincent-Salomon, A. & Poupon, M. F. A “class action” against the microenvironment: do cancer cells cooperate in metastasis? Cancer Metastasis Rev. 27, 5–10 (2008).
Solinas, G., Marchesi, F., Garlanda, C., Mantovani, A. & Allavena, P. Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev. 29, 243–248 (2010).
Francia, G., Cruz-Munoz, W., Man, S., Xu, P. & Kerbel, R. S. Mouse models of advanced spontaneous metastasis for experimental therapeutics. Nat. Rev. Cancer 11, 135–141 (2011).
Bos, P. D., Nguyen, D. X. & Massagué, J. Modeling metastasis in the mouse. Curr. Opin. Pharmacol. 10, 571–577 (2010).
Hu-Lowe, D. D. et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin. Cancer Res. 14, 7272–7283 (2008).
Schomber, T. et al. Differential effects of the vascular endothelial growth factor receptor inhibitor PTK787/ZK222584 on tumor angiogenesis and tumor lymphangiogenesis. Mol. Cancer Ther. 8, 55–63 (2009).
Yin, J. J., Zhang, L., Munasinghe, J., Linnoila, R. I. & Kelly, K. Cediranib/AZD2171 inhibits bone and brain metastasis in a preclinical model of advanced prostate cancer. Cancer Res. 70, 8662–8673 (2010).
Steeg, P. S. & Theodorescu, D. Metastasis: a therapeutic target for cancer. Nat. Clin. Pract. Oncol. 5, 206–219 (2008).
Padera, T. P. et al. Differential response of primary tumor versus lymphatic metastasis to VEGFR-2 and VEGFR-3 kinase inhibitors cediranib and vandetanib. Mol. Cancer Ther. 7, 2272–2279 (2008).
Lee, Y. J. et al. Differential effects of VEGFR-1 and VEGFR-2 inhibition on tumor metastases based on host organ environment. Cancer Res. 70, 8357–8367 (2010).
Gandhi, L. et al. Sunitinib prolongs survival in genetically engineered mouse models of multistep lung carcinogenesis. Cancer Prev. Res. (Phila) 2, 330–337 (2009).
Grandis, J. R. & Argiris, A. Targeting angiogenesis from premalignancy to metastases. Cancer Prev. Res. (Phila) 2, 291–294 (2009).
Singh, M. et al. Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models. Nat. Biotechnol. 28, 585–593 (2010).
Bose, D. et al. Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care. Lancet Oncol. 11, 373–382 (2010).
US National Institutes of Health Clinical Trials [online] , (2011).
Allegra, C. J. et al. Initial safety report of NSABP C-08: A randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer. J. Clin. Oncol. 27, 3385–3390 (2009).
Wolmark, N. et al. A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08 [abstract]. J. Clin. Oncol. 27 (Suppl.), aLBA4 (2009).
Kinoshita, T. et al. Preoperative induction with sorafenib pathologically downstaged advanced renal cell carcinoma: a case report. Int. J. Urol. 17, 286–288 (2010).
Altorki, N. et al. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer. J. Clin. Oncol. 28, 3131–3137 (2010).
Dawson, M. R., Duda, D. G., Chae, S. S., Fukumura, D. & Jain, R. K. VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation. PLoS ONE 4, e6525 (2009).
Steeg, P. S. et al. Preclinical drug development must consider the impact on metastasis. Clin. Cancer Res. 15, 4529–4530 (2009).
Francia, G. & Kerbel, R. S. Raising the bar for cancer therapy models. Nat. Biotechnol. 28, 561–562 (2010).
Hurwitz, H. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350, 2335–2342 (2004).
Giantonio, B. J. et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J. Clin. Oncol. 25, 1539–1544 (2007).
Miller, K. et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357, 2666–2676 (2007).
Miles, D. W. et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J. Clin. Oncol. 28, 3239–3247 (2010).
Robert, N. J. et al. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab (B) for first-line treatment of HER2-negative locally recurrent or metastatic breast cancer (MBC) [abstract]. J. Clin. Oncol. 27 (Suppl.), a1005 (2009).
Brufsky, A. et al. Progression-free survival (PFS) in patient subgroups in RIBBON-2, a phase III trial of chemotherapy (chemo) plus or minus bevacizumab (BV) for second-line treatment of HER2-negative, locally recurrent or metastatic breast cancer (MBC) [abstract]. J. Clin. Oncol. 28 (Suppl.), a1021 (2010).
Sandler, A. et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355, 2542–2550 (2006).
Reck, M. et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann. Oncol. 21, 1804–1809 (2010).
Kabbinavar, F. F., Miller, V. A., Johnson, B. E., O'Connor, P. G. & Soh, C. Overall survival (OS) in ATLAS, a phase IIIb trial comparing bevacizumab (B) therapy with or without erlotinib (E) after completion of chemotherapy (chemo) with B for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC) [abstract]. J. Clin. Oncol. 28 (Suppl.), a7526 (2010).
Escudier, B. et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. J. Clin. Oncol. 28, 2144–2150 (2010).
Rini, B. I. et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J. Clin. Oncol. 28, 2137–2143 (2010).
Cohen, M. H., Shen, Y. L., Keegan, P. & Pazdur, R. FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist 14, 1131–1138 (2009).
Motzer, R. J. et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 27, 3584–3590 (2009).
Goodman, V. L. et al. Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin. Cancer Res. 13, 1367–1373 (2007).
Raymond, E. et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N. Engl. J. Med. 364, 501–513 (2011).
Escudier, B. et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J. Clin. Oncol. 27, 3312–3218 (2009).
Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).
Sternberg, C. N. et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J. Clin. Oncol. 28, 1061–1068 (2010).
Herbst, R. S. et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 11, 619–626 (2010).
Hecht, J. R. et al. A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol. 27, 672–680 (2009).
Tol, J. et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N. Engl. J. Med. 360, 563–572 (2009).
Miller, K. D. et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J. Clin. Oncol. 23, 792–799 (2005).
Kang, Y. et al. AVAGAST: A randomized double-blind, placebo-controlled, phase III study of first-line capecitabine and cisplatin plus bevacizumab or placebo in patients with advanced gastric cancer (AGC) [abstract]. J. Clin. Oncol. 28 (Suppl.), aLBA4007 (2010).
Kindler, H. L. et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the cancer and Leukemia Group B (CALGB 80303). J. Clin. Oncol. 28, 3617–3622 (2010).
Van Cutsem, E. et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J. Clin. Oncol. 27, 2231–2237 (2009).
Kelly, W. K. et al. A randomized, double-blind, placebo-controlled phase III trial comparing docetaxol, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALB 90401 [abstract]. J. Clin. Oncol. 28 (Suppl.), aLBA4511 (2010).
Crown, J. et al. Phase III trial of sunitinib (SU) in combination with capecitabine (C) versus C in previously treated advanced breast cancer (ABC) [abstract]. J. Clin. Oncol. 28 (Suppl.), aLBA1011 (2010).
Barrios, C. H. et al. Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. Breast Cancer Res. Treat. 121, 121–131 (2010).
Scagliotti, G. et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J. Clin. Oncol. 28, 1835–1842 (2010).
Kohne, C. et al. Final results of CONFIRM 2: A multinational, randomized, double-blind, phase III study in 2nd line patients (pts) with metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo [abstract]. J. Clin. Oncol. 25 (Suppl.), a4033 (2007).
Natale, R. B. et al. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J. Clin. Oncol. doi: 10.1200/JCO.2010.28.5981
de Boer, R. H. et al. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J. Clin. Oncol. doi: 10.1200/JCO.2010.29.5717
Batchelor, T. T. et al. A phase III randomized study comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, with lomustine alone in recuttrent glioblastoma patients [abstract]. Ann. Oncol. 21 (Suppl. 8), aLBA7 (2010).
von Essen, C. F. Radiation enhancement of metastasis: a review. Clin. Exp. Metastasis 9, 77–104 (1991).
Kargiotis, O., Geka, A., Rao, J. S. & Kyritsis, A. P. Effects of irradiation on tumor cell survival, invasion and angiogenesis. J. Neurooncol. 100, 323–338 (2010).
Bagri, A. et al. Effects of anti-VEGF treatment duration on tumor growth, tumor regrowth, and treatment efficacy. Clin. Cancer Res. 16, 3887–3900 (2010).
Kienast, Y. et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat. Med. 16, 116–122 (2010).
Lee, S. L. et al. Hypoxia-induced pathological angiogenesis mediates tumor cell dissemination, invasion, and metastasis in a zebrafish tumor model. Proc. Natl Acad. Sci. USA 106, 19485–19490 (2009).
Ellis, L. M. & Reardon, D. A. Is there really a yin and yang to VEGF-targeted therapies? Lancet Oncol. 11, 809–811 (2010).
Van Cutsem, E., Lambrechts, D., Prenen, H., Jain, R. K. & Carmeliet, P. Lessons from the adjuvant bevacizumab trial on colon cancer: what next? J. Clin. Oncol. 29, 1–4 (2011).
Saidi, A. et al. Combined targeting of interleukin-6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness. Int. J. Cancer 125, 1054–1064 (2009).
Rofstad, E. K. & Halsør, E. F. Hypoxia-associated spontaneous pulmonary metastasis in human melanoma xenografts: involvement of microvascular hot spots induced in hypoxic foci by interleukin 8. Br. J. Cancer 86, 301–308 (2002).
Rofstad, E. K. et al. Hypoxia promotes lymph node metastasis in human melanoma xenografts by up-regulating the urokinase-type plasminogen activator receptor. Cancer Res. 62, 1847–1853 (2002).
Galluzzo, M., Pennacchietti, S., Rosano, S., Comoglio, P. M. & Michieli, P. Prevention of hypoxia by myoglobin expression in human tumor cells promotes differentiation and inhibits metastasis. J. Clin. Invest. 119, 865–875 (2009).
Cairns, R. A., Khokha, R. & Hill, R. P. Molecular mechanisms of tumor invasion and metastasis: an integrated view. Curr. Mol. Med. 3, 659–671 (2003).
Park, J. E. et al. Hypoxia tumor cell modulates its microenvironment to enhance angiogenic and metastastic potential by secretion of proteins and exosomes. Mol. Cell. Proteomics 9, 1085–1099 (2010).
Du, R. et al. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13, 206–220 (2008).
Cairns, R. A. & Hill, R. P. Acute hypoxia enhances spontaneous lymph node metastasis in an orthotopic murine model of human cervical carcinoma. Cancer Res. 64, 2054–2061 (2004).
Cairns, R. A., Kalliomaki, T. & Hill, R. P. Acute (cyclic) hypoxia enhances spontaneous metastasis of KHT murine tumors. Cancer Res. 61, 8903–8908 (2001).
Rofstad, E. K., Gaustad, J. V., Egeland, T. A., Mathiesen, B. & Galappathi, K. Tumors exposed to acute cyclic hypoxic stress show enhanced angiogenesis, perfusion and metastatic dissemination. Int. J. Cancer 127, 1535–1546 (2010).
Higgins, D. F. et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J. Clin. Invest. 117, 3810–3820 (2007).
Casanovas, O., Hicklin, D. J., Bergers, G. & Hanahan, D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8, 299–309 (2005).
Martinez-Outschoorn, U. E. et al. The autophagic tumor stroma model of cancer or “battery-operated tumor growth”: A simple solution to the autophagy paradox. Cell Cycle 9, 4297–4306 (2010).
Ricci-Vitiani, L. et al. Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468, 824–828 (2010).
Wang, R. et al. Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468, 829–833 (2010).
Crawford, Y. et al. PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15, 21–34 (2009).
Ebos, J. M., Lee, C. R., Christensen, J. G., Mutsaers, A. J. & Kerbel, R. S. Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc. Natl Acad. Sci. USA 104, 17069–17074 (2007).
Batchelor, T. T. et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11, 83–95 (2007).
Lewis, C. E., De Palma, M. & Naldini, L. Tie2-expressing monocytes and tumor angiogenesis: regulation by hypoxia and angiopoietin-2. Cancer Res. 67, 8429–8432 (2007).
Shojaei, F. et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat. Biotechnol. 25, 911–920 (2007).
Joyce, J. A. & Pollard, J. W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer 9, 239–252 (2009).
Shojaei, F. et al. G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc. Natl Acad. Sci. USA 106, 6742–6747 (2009).
Kaplan, R. N. et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438, 820–827 (2005).
Bergers, G., Song, S., Meyer-Morse, N., Bergsland, E. & Hanahan, D. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J. Clin. Invest. 111, 1287–1295 (2003).
Hirschi, K. K. & D'Amore, P. A. Control of angiogenesis by the pericyte: molecular mechanisms and significance. EXS 79, 419–428 (1997).
Elice, F., Rodeghiero, F., Falanga, A. & Rickles, F. R. Thrombosis associated with angiogenesis inhibitors. Best. Pract. Res. Clin. Haematol. 22, 115–128 (2009).