The new paradigm in the treatment of colorectal cancer: are we hitting the right target?

Bibliography

• FOLKMAN J: What is the evidence that tumors are angiogenesis dependent? J. Natl. Cancer Inst. (1990) 82(1):4-6.
   PubMed Web of Science ®Google Scholar
• FOLKMAN J: Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. (1971) 285(21):1182-1186.
   PubMed Web of Science ®Google Scholar
• HANAHAN D, FOLKMAN J: Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell (1996) 86(3):353-364.
   PubMed Web of Science ®Google Scholar
• HANAHAN D, WEINBERG RA: The hallmarks of cancer. Cell (2000) 100(1):57-70.
   PubMed Web of Science ®Google Scholar
• KIM KJ, LI B, WINER J et al.: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature (1993) 362(6423):841-844.
   PubMed Web of Science ®Google Scholar
• FERRARA N: Vascular endothelial growth factor: basic science and clinical progress. Endocr. Rev. (2004) 25(4):581-611.
   PubMed Web of Science ®Google Scholar
• ELLIS LM, TAKAHASHI Y, LIU W, SHAHEEN RM: Vascular endothelial growth factor in human colon cancer: biology and therapeutic implications. Oncologist (2000) 5(Suppl. 1):11-15.
   PubMedGoogle Scholar
• GEORGE ML, TUTTON MG, JANSSEN F et al.: VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia (2001) 3(5):420-427.
   PubMed Web of Science ®Google Scholar
• YAMAMORI M, SAKAEDA T, NAKAMURA T et al.: Association of VEGF genotype with mRNA level in colorectal adenocarcinomas. Biochem. Biophys. Res. Commun. (2004) 325(1):144-150.
   PubMed Web of Science ®Google Scholar
• ISHIGAMI SI, ARII S, FURUTANI M et al.: Predictive value of vascular endothelial growth factor (VEGF) in metastasis and prognosis of human colorectal cancer. Br. J. Cancer (1998) 78(10):1379-1384.
   Web of Science ®Google Scholar
• MARGOLIN K, GORDON MS, HOLMGREN E et al.: Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data. J. Clin. Oncol. (2001) 19(3):851-856.
   PubMed Web of Science ®Google Scholar
• KABBINAVAR F, HURWITZ HI, FEHRENBACHER L et al.: Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J. Clin. Oncol. (2003) 21(1):60-65.
   PubMed Web of Science ®Google Scholar
• HURWITZ H, FEHRENBACHER L, NOVOTNY W et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. (2004) 350(23):2335-2342.
   PubMed Web of Science ®Google Scholar
• GIANTONIO BJ: Bevacizumab in the treatment of metastatic colorectal cancer (mCRC) in second- and third-line settings. Semin. Oncol. (2006) 33(5 Suppl. 10):S15-S18.
   PubMed Web of Science ®Google Scholar
• GIANTONIO B, CATALANO P, O’DWYER P, MEROPOL N, BENSON AB III: Impact of bevacizumab dose reduction on clinical outcomes for patients treated on the Eastern Cooperative Oncology Group’s Study E3200. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3538 (Abstract).
   Google Scholar
• HOCHSTER H, HART L, RAMANATHAN R: Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): final analysis of the TREE-study. ASCO Annual Meeting Proceedings (2006) 24(18S):3510 (Abstract).
   Google Scholar
• SALTZ L, LENZ H, HOCHSTER H: Randomized Phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer. J. Clin. Oncol. (Meeting Abstracts) (2005) 23(16S):3508 (Abstract).
   Google Scholar
• WOOD JM, BOLD G, BUCHDUNGER E et al.: PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. (2000) 60(8):2178-2189.
   PubMed Web of Science ®Google Scholar
• DREVS J, HOFMANN I, HUGENSCHMIDT H et al.: Effects of PTK787/ZK 222584, a specific inhibitor of vascular endothelial growth factor receptor tyrosine kinases, on primary tumor, metastasis, vessel density, and blood flow in a murine renal cell carcinoma model. Cancer Res. (2000) 60(17):4819-4824.
   PubMed Web of Science ®Google Scholar
• MORGAN B, THOMAS AL, DREVS J et al.: Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two Phase I studies. J. Clin. Oncol. (2003) 21(21):3955-3964.
   PubMed Web of Science ®Google Scholar
• SCHLEUCHER N, TRARBACH T, JUNKER U et al.: Phase I/II study of PTZ787/ZK222584 (PTK/ZK), a novel, oral angiogenesis inhibitor in combination with FOLFIRI as first-line treatment of patients with metastatic colorectal cancer. J. Clin. Oncol. (Meeting Abstracts) (2004) 22(14S):3558 (Abstract).
   PubMed Web of Science ®Google Scholar
• STEWARD W, THOMAS A, MORGAN B: Expanded Phase I/II study of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with FOLFOX-4 as first-line treatment for patients with metastatic colorectal cancer. J. Clin. Oncol. (Meeting Abstracts) (2004) 22(14S):3556 (Abstract).
   Google Scholar
• HECHT J, TRARBACH T: A randomized, double-blind, placebo-controlled, Phase III study in patients (Pts) with metastatic adenocarcinoma of the colon or rectum receiving first-line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin and PTK787/ZK 222584 or placebo (CONFIRM-1). J. Clin. Oncol. (Meeting Abstracts) (2005) 23(16S):3 (Abstract).
   Web of Science ®Google Scholar
• KOEHNE C, BAJETTA E, LIN E: Results of an interim analysis of a multinational randomized, double-blind, Phase III study in patients (pts) with previously treated metastatic colorectal cancer (mCRC) receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo (CONFIRM 2). J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3508 (Abstract).
   PubMed Web of Science ®Google Scholar
• HUANG J, SOFFER SZ, KIM ES et al.: Vascular remodeling marks tumors that recur during chronic suppression of angiogenesis. Mol. Cancer Res. (2004) 2(1):36-42.
   PubMed Web of Science ®Google Scholar
• HICKLIN DJ, ELLIS LM: Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol. (2005) 23(5):1011-1027.
   PubMed Web of Science ®Google Scholar
• WEDGE SR, OGILVIE DJ, DUKES M et al.: ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. (2002) 62(16):4645-4655.
   PubMed Web of Science ®Google Scholar
• TROIANI T, LOCKERBIE O, MORROW M: ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases, blocks VEGF-C-induced activation of VEGFR-3 and cell proliferation in human colon cancer cell lines. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):13171 (Abstract).
   Google Scholar
• MORELLI MP, CASCONE T, TROIANI T et al.: Anti-tumor activity of the combination of cetuximab, an anti-EGFR blocking monoclonal antibody and ZD6474, an inhibitor of VEGFR and EGFR tyrosine kinases. J. Cell. Physiol. (2006) 208(2):344-353.
   PubMed Web of Science ®Google Scholar
• LORUSSO P, HEATH E, VALDIVIESO M: Phase I evaluation of AZD2171, a highly potent and selective inhibitor of VEGFR signaling, in combination with selected chemotherapy regimens in patients with advanced solid tumors. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3034 (Abstract).
   Google Scholar
• MENDEL DB, LAIRD AD, XIN X et al.: In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res. (2003) 9(1):327-337.
   PubMed Web of Science ®Google Scholar
• MORIMOTO AM, TAN N, WEST K et al.: Gene expression profiling of human colon xenograft tumors following treatment with SU11248, a multitargeted tyrosine kinase inhibitor. Oncogene (2004) 23(8):1618-1626.
   PubMed Web of Science ®Google Scholar
• LENZ H, MARSHALL J, ROSEN L: Phase II trial of SU11248 in patients with metastatic colorectal cancer (MCRC) after failure of standard chemotherapy. Proceedings of ASCO Gastrointestinal Cancer Symposium (2006):240 (Abstract).
   Google Scholar
• MARZOLA P, DEGRASSI A, CALDERAN L et al.: In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. Clin. Cancer Res. (2004) 10(2):739-750.
   PubMed Web of Science ®Google Scholar
• DAVIS DW, TAKAMORI R, RAUT CP et al.: Pharmacodynamic analysis of target inhibition and endothelial cell death in tumors treated with the vascular endothelial growth factor receptor antagonists SU5416 or SU6668. Clin. Cancer Res. (2005) 11(2 Part 1):678-689.
   PubMed Web of Science ®Google Scholar
• MULAY M, LIMENTANI S, CARROLL M, FURFINE E: Safety and pharmacokinetics of intravenous VEGF Trap plus FOLFOX4 in a combination Phase I clinical trial of patients with advanced solid tumors. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):13061 (Abstract).
   Google Scholar
• COHEN SJ, COHEN RB, MEROPOL NJ: Targeting signal transduction pathways in colorectal cancer-more than skin deep. J. Clin. Oncol. (2005) 23(23):5374-5385.
   PubMed Web of Science ®Google Scholar
• MENDELSOHN J, BASELGA J: Epidermal growth factor receptor targeting in cancer. Semin. Oncol. (2006) 33(4):369-385.
   PubMed Web of Science ®Google Scholar
• BASELGA J, ARTEAGA CL: Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J. Clin. Oncol. (2005) 23(11):2445-2459.
   PubMed Web of Science ®Google Scholar
• HARARI PM: Epidermal growth factor receptor inhibition strategies in oncology. Endocr. Relat. Cancer (2004) 11(4):689-708.
   PubMed Web of Science ®Google Scholar
• CUNNINGHAM D, HUMBLET Y, SIENA S et al.: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. (2004) 351(4):337-345.
   PubMed Web of Science ®Google Scholar
• SALTZ L: Epidermal growth factor receptor-negative colorectal cancer: is there truly such an entity? Clin. Colorectal Cancer (2005) 5(Suppl. 2):S98-S100.
   PubMedGoogle Scholar
• MALIK S, HECHT J, PATNAIK A: Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). J. Clin. Oncol. (Meeting Abstracts) (2005) 23(16S):3520 (Abstract).
   Google Scholar
• BERLIN J, NEUBAUER M, SWANSON P et al.: Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing > = 10% epidermal growth factor receptor (EGFr). J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3548 (Abstract).
   PubMed Web of Science ®Google Scholar
• ARENDS R, YANG BB, SCHWAB G et al.: Flexible dosing schedules of panitumumab (ABX-EGF) in cancer patients. J. Clin. Oncol. (Meeting Abstracts) (2005) 23(16S):3089 (Abstract).
   Google Scholar
• HECHT J, MITCHELL E, BARANDA J: Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing low (1–9%) or negative (< 1%) levels of epidermal growth factor receptor (EGFr). J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3547 (Abstract).
   Google Scholar
• WAINBERG Z, HECHT JR: A Phase III randomized, open-label, controlled trial of chemotherapy and bevacizumab with or without panitumumab in the first-line treatment of patients with metastatic colorectal cancer. Clin. Colorectal Cancer (2006) 5(5):363-367.
   PubMed Web of Science ®Google Scholar
• SALTZ LB, MEROPOL NJ, LOEHRER PJ et al.: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J. Clin. Oncol. (2004) 22(7):1201-1208.
   PubMed Web of Science ®Google Scholar
• VANHOEFER U, TEWES M, ROJO F et al.: Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J. Clin. Oncol. (2004) 22(1):175-184.
   PubMed Web of Science ®Google Scholar
• MAMOT C, RITSCHARD R, KUNG W et al.: EGFR-targeted immunoliposomes derived from the monoclonal antibody EMD72000 mediate specific and efficient drug delivery to a variety of colorectal cancer cells. J. Drug Target. (2006) 14(4):215-223.
   PubMed Web of Science ®Google Scholar
• DORLIGSCHAW O, KEGEL T, JORDAN K, AL E: ZD 1839 (Iressa)-based treatment as last-line therapy in patients with advanced colorectal cancer. Proceedings of American Association for Cancer Research (2003):1494 (Abstract).
   Google Scholar
• HIDALGO M, SIU LL, NEMUNAITIS J et al.: Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J. Clin. Oncol. (2001) 19(13):3267-3279.
   PubMed Web of Science ®Google Scholar
• MESSERSMITH WA, LAHERU DA, SENZER NN et al.: Phase I trial of irinotecan, infusional 5-fluorouracil, and leucovorin (FOLFIRI) with erlotinib (OSI-774): early termination due to increased toxicities. Clin. Cancer Res. (2004) 10(19):6522-6527.
   PubMed Web of Science ®Google Scholar
• DELORD J, BEALE P, VAN CUTSEM E et al.: A Phase Ib dose-escalation trial of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer (MCRC) patients. J. Clin. Oncol. (Meeting Abstracts) (2004) 22(14S):3585 (Abstract).
   Google Scholar
• KUO T, CHO CD, HALSEY J et al.: Phase II study of gefitinib, fluorouracil, leucovorin, and oxaliplatin therapy in previously treated patients with metastatic colorectal cancer. J. Clin. Oncol. (2005) 23(24):5613-5619.
   PubMed Web of Science ®Google Scholar
• MEYERHARDT JA, ZHU AX, ENZINGER PC et al.: Phase II study of capecitabine, oxaliplatin, and erlotinib in previously treated patients with metastastic colorectal cancer. J. Clin. Oncol. (2006) 24(12):1892-1897.
   PubMed Web of Science ®Google Scholar
• WEBER MM, FOTTNER C, LIU SB et al.: Overexpression of the insulin-like growth factor I receptor in human colon carcinomas. Cancer (2002) 95(10):2086-2095.
   PubMed Web of Science ®Google Scholar
• REMACLE-BONNET MM, GARROUSTE FL, HELLER S et al.: Insulin-like growth factor-I protects colon cancer cells from death factor-induced apoptosis by potentiating tumor necrosis factor α-induced mitogen-activated protein kinase and nuclear factor κB signaling pathways. Cancer Res. (2000) 60(7):2007-2017.
   PubMed Web of Science ®Google Scholar
• REINMUTH N, LIU W, FAN F et al.: Blockade of insulin-like growth factor I receptor function inhibits growth and angiogenesis of colon cancer. Clin. Cancer Res. (2002) 8(10):3259-3269.
   PubMed Web of Science ®Google Scholar
• BAUER T, MCCARTY M, WEY J et al.: Combination therapy with insulin-like growth factor-I receptor (IGF-IR) antibody plus oxaliplatin decreases hepatic growth of human colon cancer. Proceedings of ASCO Gastrointestinal Cancer Symposium (2004):279 (Abstract).
   Google Scholar
• LU D, ZHANG H, KOO H et al.: A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumor activity. J. Biol. Chem. (2005) 280(20):19665-19672.
   PubMed Web of Science ®Google Scholar
• COHEN BD, BAKER DA, SODERSTROM C et al.: Combination therapy enhances the inhibition of tumor growth with the fully human anti-type 1 insulin-like growth factor receptor monoclonal antibody CP-751,871. Clin. Cancer Res. (2005) 11(5):2063-2073.
   PubMed Web of Science ®Google Scholar
• TAKAHASHI Y, BUCANA CD, LIU W et al.: Platelet-derived endothelial cell growth factor in human colon cancer angiogenesis: role of infiltrating cells. J. Natl. Cancer Inst. (1996) 88(16):1146-1151.
   PubMed Web of Science ®Google Scholar
• HSU S, HUANG F, FRIEDMAN E: Platelet-derived growth factor-B increases colon cancer cell growth in vivo by a paracrine effect. J. Cell. Physiol. (1995) 165(2):239-245.
   PubMed Web of Science ®Google Scholar
• PIETRAS K, SJOBLOM T, RUBIN K, HELDIN CH, OSTMAN A: PDGF receptors as cancer drug targets. Cancer Cell (2003) 3(5):439-443.
   PubMed Web of Science ®Google Scholar
• 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. (2003) 111(9):1287-1295.
   PubMed Web of Science ®Google Scholar
• ATTOUB S, RIVAT C, RODRIGUES S et al.: The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. Cancer Res. (2002) 62(17):4879-4883.
   PubMed Web of Science ®Google Scholar
• RAO S, CUNNINGHAM D, DE GRAMONT A et al.: Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. J. Clin. Oncol. (2004) 22(19):3950-3957.
   PubMed Web of Science ®Google Scholar
• SHARMA S, KEMENY N, KELSEN DP et al.: A Phase II trial of farnesyl protein transferase inhibitor SCH 66336, given by twice-daily oral administration, in patients with metastatic colorectal cancer refractory to 5-fluorouracil and irinotecan. Ann. Oncol. (2002) 13(7):1067-1071.
   PubMed Web of Science ®Google Scholar
• SALEH M, POSEY J, PLEASANT L, AL A: A Phase II trial of ISIS 2503, an antisense inhibitor of H-ras, as first line therapy for advanced colorectal carcinoma. Proc. Am. Soc. Clin. Oncol. (2000) 19:1258 (Abstract).
   Google Scholar
• NAGASAKA T, SASAMOTO H, NOTOHARA K et al.: Colorectal cancer with mutation in BRAF, KRAS, and wild-type with respect to both oncogenes showing different patterns of DNA methylation. J. Clin. Oncol. (2004) 22(22):4584-4594.
   PubMed Web of Science ®Google Scholar
• CRIPPS MC, FIGUEREDO AT, OZA AM et al.: Phase II randomized study of ISIS 3521 and ISIS 5132 in patients with locally advanced or metastatic colorectal cancer: a National Cancer Institute of Canada clinical trials group study. Clin. Cancer Res. (2002) 8(7):2188-2192.
   PubMed Web of Science ®Google Scholar
• WILHELM SM, CARTER C, TANG L et al.: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. (2004) 64(19):7099-7109.
   PubMed Web of Science ®Google Scholar
• STRUMBERG D, RICHLY H, HILGER RA et al.: Phase I clinical and pharmacokinetic study of the novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J. Clin. Oncol. (2005) 23(5):965-972.
   PubMed Web of Science ®Google Scholar
• AMERY W, DONY J: A clinical trial design avoiding undue placebo treatment. J. Clin. Pharmacol. (1975) 15(10):674-679.
   PubMed Web of Science ®Google Scholar
• RATAIN MJ, EISEN T, STADLER WM et al.: Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. (2006) 24(16):2505-2512.
   PubMed Web of Science ®Google Scholar
• MROSS K, STEINBILD S, BAAS F et al.: Drug–drug interaction pharmacokinetic study with the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with irinotecan (CPT-11) in patients with solid tumors. Int. J. Clin. Pharmacol. Ther. (2003) 41(12):618-619.
   PubMedGoogle Scholar
• KUPSCH P, HENNING BF, PASSARGE K et al.: Results of a Phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. Clin. Colorectal Cancer (2005) 5(3):188-196.
   PubMedGoogle Scholar
• HOSHINO R, CHATANI Y, YAMORI T et al.: Constitutive activation of the 41-/43-kDa mitogen-activated protein kinase signaling pathway in human tumors. Oncogene (1999) 18(3):813-822.
   Google Scholar
• SEBOLT-LEOPOLD JS, DUDLEY DT, HERRERA R et al.: Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med. (1999) 5(7):810-816.
   PubMed Web of Science ®Google Scholar
• RINEHART J, ADJEI AA, LORUSSO PM et al.: Multicenter Phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J. Clin. Oncol. (2004) 22(22):4456-4462.
   PubMed Web of Science ®Google Scholar
• LEE P, E. W, YEH T, AL E: ARRY-142886, a potent and selective MEK inhibitor: efficacy in murine xenograft models correlates with decreased ERK phosphorylation. Proc. Am. Assoc. Cancer Res. (2004) 45:3890 (Abstract).
   Google Scholar
• BADER AG, KANG S, ZHAO L, VOGT PK: Oncogenic PI3K deregulates transcription and translation. Nat. Rev. Cancer (2005) 5(12):921-929.
   PubMed Web of Science ®Google Scholar
• CLARK AS, WEST K, STREICHER S, DENNIS PA: Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol. Cancer Ther. (2002) 1(9):707-717.
   PubMed Web of Science ®Google Scholar
• SEMBA S, ITOH N, ITO M, HARADA M, YAMAKAWA M: The in vitro and in vivo effects of 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), a specific inhibitor of phosphatidylinositol 3′-kinase, in human colon cancer cells. Clin. Cancer Res. (2002) 8(6):1957-1963.
   PubMed Web of Science ®Google Scholar
• IHLE NT, WILLIAMS R, CHOW S et al.: Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling. Mol. Cancer Ther. (2004) 3(7):763-772.
   PubMed Web of Science ®Google Scholar
• GENG L, TAN J, HIMMELFARB E et al.: A specific antagonist of the p110δ catalytic component of phosphatidylinositol 3′-kinase, IC486068, enhances radiation-induced tumor vascular destruction. Cancer Res. (2004) 64(14):4893-4899.
   PubMed Web of Science ®Google Scholar
• FUJIWARA H, MATSUNAGA K, SAITO M et al.: Halenaquinone, a novel phosphatidylinositol 3-kinase inhibitor from a marine sponge, induces apoptosis in PC12 cells. Eur. J. Pharmacol. (2001) 413(1):37-45.
   PubMed Web of Science ®Google Scholar
• ALIGAYER H, BOYD DD, HEISS MM et al.: Activation of Src kinase in primary colorectal carcinoma: an indicator of poor clinical prognosis. Cancer (2002) 94(2):344-351.
   PubMed Web of Science ®Google Scholar
• CAO X, TAY A, GUY GR, TAN YH: Activation and association of Stat3 with Src in v-Src-transformed cell lines. Mol. Cell. Biol. (1996) 16(4):1595-1603.
   PubMed Web of Science ®Google Scholar
• BRUNTON VG, AVIZIENYTE E, FINCHAM VJ et al.: Identification of Src-specific phosphorylation site on focal adhesion kinase: dissection of the role of Src SH2 and catalytic functions and their consequences for tumor cell behavior. Cancer Res. (2005) 65(4):1335-1342.
   PubMed Web of Science ®Google Scholar
• O’HARE T, POLLOCK R, STOFFREGEN EP et al.: Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood (2004) 104(8):2532-2539.
   PubMed Web of Science ®Google Scholar
• SERRELS A, MACPHERSON IR, EVANS TR et al.: Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib. Mol. Cancer Ther. (2006) 5(12):3014-3022.
   PubMed Web of Science ®Google Scholar
• HENNEQUIN LF, ALLEN J, BREED J et al.: N-(5-chloro-1,3-benzodioxol-4-yl)- 7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin- 4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. J. Med. Chem. (2006) 49(22):6465-6488.
   PubMed Web of Science ®Google Scholar
• COLUCCIA AM, BENATI D, DEKHIL H et al.: SKI-606 decreases growth and motility of colorectal cancer cells by preventing pp60 (c-Src)-dependent tyrosine phosphorylation of β-catenin and its nuclear signaling. Cancer Res. (2006) 66(4):2279-2286.
   PubMed Web of Science ®Google Scholar
• GOLAS JM, LUCAS J, ETIENNE C et al.: SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft models. Cancer Res. (2005) 65(12):5358-5364.
   PubMed Web of Science ®Google Scholar
• MA XT, WANG S, YE YJ et al.: Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma. World J. Gastroenterol. (2004) 10(11):1569-1573.
   PubMed Web of Science ®Google Scholar
• RIVAT C, RODRIGUES S, BRUYNEEL E et al.: Implication of STAT3 signaling in human colonic cancer cells during intestinal trefoil factor 3 (TFF3) – and vascular endothelial growth factor-mediated cellular invasion and tumor growth. Cancer Res. (2005) 65(1):195-202.
   PubMed Web of Science ®Google Scholar
• RUBIN E, SHAPIRO G, STEIN M, AL E: A Phase I clinical and pharmacokinetic (PK) trial of the Aurora kinase (AK) inhibitor MK-0457 in cancer patients. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3009 (Abstract).
   Google Scholar
• KEEN N, TAYLOR S: Aurora-kinase inhibitors as anticancer agents. Nat. Rev. Cancer (2004) 4(12):927-936.
   PubMed Web of Science ®Google Scholar
• BISCHOFF JR, ANDERSON L, ZHU Y et al.: A homologue of Drosophila Aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. (1998) 17(11):3052-3065.
   PubMed Web of Science ®Google Scholar
• HARRINGTON EA, BEBBINGTON D, MOORE J et al.: VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat. Med. (2004) 10(3):262-267.
   PubMed Web of Science ®Google Scholar
• STRATER J, HINZ U, WALCZAK H et al.: Expression of TRAIL and TRAIL receptors in colon carcinoma: TRAIL-R1 is an independent prognostic parameter. Clin. Cancer Res. (2002) 8(12):3734-3740.
   PubMed Web of Science ®Google Scholar
• NAKA T, SUGAMURA K, HYLANDER BL et al.: Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients’ colon tumors grown in SCID mice. Cancer Res. (2002) 62(20):5800-5806.
   PubMed Web of Science ®Google Scholar
• GROSS A, MCDONNELL JM, KORSMEYER SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. (1999) 13(15):1899-1911.
   PubMed Web of Science ®Google Scholar
• MITA MM, OCHOA L, ROWINSKY EK et al.: A Phase I, pharmacokinetic and biologic correlative study of oblimersen sodium (Genasense, G3139) and irinotecan in patients with metastatic colorectal cancer. Ann. Oncol. (2006) 17(2):313-321.
   PubMed Web of Science ®Google Scholar
• MARINI P, DENZINGER S, SCHILLER D et al.: Combined treatment of colorectal tumours with agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and radiotherapy: enhanced effects in vitro and dose-dependent growth delay in vivo. Oncogene (2006) 25(37):5145-5154.
   PubMed Web of Science ®Google Scholar
• SALCEDO T, ALDERSON R, BASU S, AL E: TRM-1, a human TRAIL-R1 agonistic monoclonal antibody. displays in vitro and in vivo anti-tumor activity. Proc. Am. Assoc. Cancer Res. (2002):4240 (Abstract).
   Google Scholar
• PUKAC L, KANAKARAJ P, HUMPHREYS R et al.: HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo. Br. J. Cancer (2005) 92(8):1430-1441.
   PubMed Web of Science ®Google Scholar
• CHO B, CHOI H, JEUNG H, AL E: Phase II study of oral S-1 monotherapy in metastatic colorectal cancer after failure of both irinotecana nd oxaliplatin-containinig regimen. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3597 (Abstract).
   PubMed Web of Science ®Google Scholar
• KOMATSU Y, YUUKI S, FUSE N et al.: Phase II study of oral S-1 plus irinotecan in patients with advanced colorectal cancer: Hokkaido Gastrointestinal Cancer Study Group HGCSG0302. Jpn J. Clin. Oncol. (2005) 35(2):88-89.
   PubMed Web of Science ®Google Scholar
• MOORE MJ, JONES C, HARKER G, AL E: Phase II trial of DJ-927, an oral tubulin depolymerization inhibitor, in the treatment of metastatic colorectal cancer. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3591 (Abstract).
   Google Scholar
• FAKIH M, PENDYALA L, TOTH K, CREAVEN P: A Phase I study of voristat (suberoylanilide hydroxamic acid, SAHA) in combination with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in patients with advanced colorectal cancer. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3592 (Abstract).
   Google Scholar
• WHITEHEAD RP, MCCOY S, WOLLNER I, AL E: Phase II trial of depsipeptide (NSC-630176) in colorectal cancer patients who have received either one or two prior chemotherapy regimens for metastatic or locally advanced, unresectable disease: a Southwest Oncology Group study. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3598 (Abstract).
   Google Scholar
• LEE FY, BORZILLERI R, FAIRCHILD CR et al.: BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin. Cancer Res. (2001) 7(5):1429-1437.
   PubMed Web of Science ®Google Scholar
• ENG C, KINDLER HL, NATTAM S et al.: A Phase II trial of the epothilone B analog, BMS-247550, in patients with previously treated advanced colorectal cancer. Ann. Oncol. (2004) 15(6):928-932.
   PubMed Web of Science ®Google Scholar
• EL-KHOUEIRY A, IQBAL S, SINGH D, AL E: A randomized Phase II non-comparative study of ispinesib given weekly or every three weeks in metastatic colorectal cancer. J. Clin. Oncol. (Meeting Abstracts) (2006) 24(18S):3595 (Abstract).
   Google Scholar