Dasatinib + Gefitinib, a non platinum-based combination with enhanced growth inhibitory, anti-migratory and anti-invasive potency against human ovarian cancer cells

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet. 2009;374:1371–82.

Jelovac D, Armstrong DK. Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011;61:183–203.

Kohler M, Janz I, Wintzer HO, Wagner E, Bauknecht T. The expression of EGF receptors, EGF-like factors and c-myc in ovarian and cervical carcinomas and their potential clinical significance. Anticancer Res. 1989;9:1537–47.

Kohler M, Bauknecht T, Grimm M, Birmelin G, Kommoss F, Wagner E. Epidermal growth factor receptor and transforming growth factor alpha expression in human ovarian carcinomas. Eur J Cancer. 1992;28A:1432–7.

Psyrri A, Kassar M, Yu Z, et al. Effect of epidermal growth factor receptor expression level on survival in patients with epithelial ovarian cancer. Clin Cancer Res. 2005;11:8637–43.

Wiener JR, Windham TC, Estrella VC, et al. Activated SRC protein tyrosine kinase is overexpressed in late-stage human ovarian cancers. Gynecol Oncol. 2003;88:73–9.

Teoh D, Ayeni TA, Rubatt JM, et al. Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells. Gynecol Oncol. 2011;121:187–92.

Konecny GE, Glas R, Dering J, et al. Activity of the multikinase inhibitor dasatinib against ovarian cancer cells. Br J Cancer. 2009;101:1699–708.

Marchion DC, Bicaku E, Xiong Y, et al. A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013;29:2011–8.

Li E, Hu Z, Sun Y, et al. Small molecule inhibitor of c-Met (PHA665752) suppresses the growth of ovarian cancer cells and reverses cisplatin resistance. Tumour Biol. 2015;37:7843:52.

Summy JM, Gallick GE. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 2003;22:337–58.

Peruzzi B, Bottaro DP. Targeting the c-Met signaling pathway in cancer. Clin Cancer Res. 2006;12:3657–60.

Yewale C, Baradia D, Vhora I, Patil S, Misra A. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013;34:8690–707.

Sasaki T, Hiroki K, Yamashita Y. The role of epidermal growth factor receptor in cancer metastasis and microenvironment. Biomed Res Int. 2013;2013:546318.

Schilder RJ, Sill MW, Chen X, et al. Phase II study of gefitinib in patients with relapsed or persistent ovarian or primary peritoneal carcinoma and evaluation of epidermal growth factor receptor mutations and immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res. 2005;11:5539–48.

Glaysher S, Bolton LM, Johnson P, et al. Targeting EGFR and PI3K pathways in ovarian cancer. Br J Cancer. 2013;109:1786–94.

Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene. 2000;19:5636–42.

Parsons JT, Parsons SJ. Src family protein tyrosine kinases: cooperating with growth factor and adhesion signaling pathways. Curr Opin Cell Biol. 1997;9:187–92.

Wiener JR, Nakano K, Kruzelock RP, Bucana CD, Bast Jr RC, Gallick GE. Decreased Src tyrosine kinase activity inhibits malignant human ovarian cancer tumor growth in a nude mouse model. Clin Cancer Res. 1999;5:2164–70.

Han LY, Landen CN, Trevino JG, et al. Antiangiogenic and antitumor effects of SRC inhibition in ovarian carcinoma. Cancer Res. 2006;66:8633–9.

McNeish IA, Ledermann JA, Webber L, et al. A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancerdagger. Ann Oncol. 2014;25:1988–95.

Secord AA, Teoh DK, Barry WT, et al. A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Clin Cancer Res. 2012;18:5489–98.

Ayhan A, Ertunc D, Tok EC, Ayhan A. Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance. Int J Gynecol Cancer. 2005;15:618–23.

Sawada K, Radjabi AR, Shinomiya N, et al. c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer Res. 2007;67:1670–9.

Mariani M, McHugh M, Petrillo M, et al. HGF/c-Met axis drives cancer aggressiveness in the neo-adjuvant setting of ovarian cancer. Oncotarget. 2014;5:4855–67.

Zillhardt M, Christensen JG, Lengyel E. An orally available small-molecule inhibitor of c-Met, PF-2341066, reduces tumor burden and metastasis in a preclinical model of ovarian cancer metastasis. Neoplasia. 2010;12:1–10.

Zillhardt M, Park SM, Romero IL, et al. Foretinib (GSK1363089), an orally available multikinase inhibitor of c-Met and VEGFR-2, blocks proliferation, induces anoikis, and impairs ovarian cancer metastasis. Clin Cancer Res. 2011;17:4042–51.

Stabile LP, He G, Lui VW, et al. c-Src activation mediates erlotinib resistance in head and neck cancer by stimulating c-Met. Clin Cancer Res. 2013;19:380–92.

Jo M, Stolz DB, Esplen JE, Dorko K, Michalopoulos GK, Strom SC. Cross-talk between epidermal growth factor receptor and c-Met signal pathways in transformed cells. J Biol Chem. 2000;275:8806–11.

Yano S, Wang W, Li Q, et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations. Cancer Res. 2008;68:9479–87.

Leu TH, Maa MC. Functional implication of the interaction between EGF receptor and c-Src. Front Biosci. 2003;8:s28–38.

Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990;82:1107–12.

Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzym Regul. 1984;22:27–55.

Heitz F, Harter P, Barinoff J, et al. Bevacizumab in the treatment of ovarian cancer. Adv Ther. 2012;29:723–35.

Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366:1382–92.

Huang F, Reeves K, Han X, et al. Identification of candidate molecular markers predicting sensitivity in solid tumors to dasatinib: rationale for patient selection. Cancer Res. 2007;67:2226–38.

Han Y, Xu JM, Duan HQ, Zhang Y, Liu XQ, Zhang JS. Correlation of epidermal growth factor receptor mutations and HER2/3 protein expression with clinical outcome in advanced non-small cell lung cancer patients treated with gefitinib. Chin J Cancer. 2010;29:69–75.

Han SW, Hwang PG, Chung DH, et al. Epidermal growth factor receptor (EGFR) downstream molecules as response predictive markers for gefitinib (Iressa, ZD1839) in chemotherapy-resistant non-small cell lung cancer. Int J Cancer. 2005;113:109–15.

McDermott U, Settleman J. Personalized cancer therapy with selective kinase inhibitors: an emerging paradigm in medical oncology. J Clin Oncol. 2009;27:5650–9.

Tracy S, Mukohara T, Hansen M, Meyerson M, Johnson BE, Janne PA. Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res. 2004;64:7241–4.

Ariyama H, Qin B, Baba E, et al. Gefitinib, a selective EGFR tyrosine kinase inhibitor, induces apoptosis through activation of Bax in human gallbladder adenocarcinoma cells. J Cell Biochem. 2006;97:724–34.

Shor AC, Keschman EA, Lee FY, et al. Dasatinib inhibits migration and invasion in diverse human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on SRC kinase for survival. Cancer Res. 2007;67:2800–8.

Johnson FM, Saigal B, Talpaz M, Donato NJ. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells. Clin Cancer Res. 2005;11:6924–32.

Elkind NB, Szentpetery Z, Apati A, et al. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib). Cancer Res. 2005;65:1770–7.

Hara F, Aoe M, Doihara H, et al. Antitumor effect of gefitinib (‘Iressa’) on esophageal squamous cell carcinoma cell lines in vitro and in vivo. Cancer Lett. 2005;226:37–47.

Le XF, Mao W, Lu Z, Carter BZ, Bast Jr RC. Dasatinib induces autophagic cell death in human ovarian cancer. Cancer. 2010;116:4980–90.

Timeus F, Crescenzio N, Fandi A, Doria A, Foglia L, di Cordero ML. In vitro antiproliferative and antimigratory activity of dasatinib in neuroblastoma and Ewing sarcoma cell lines. Oncol Rep. 2008;19:353–9.

Buettner R, Mesa T, Vultur A, Lee F, Jove R. Inhibition of Src family kinases with dasatinib blocks migration and invasion of human melanoma cells. Mol Cancer Res. 2008;6:1766–74.

Pichot CS, Hartiq SM, Xia L, et al. Dasatinib synergizes with doxorubicin to block growth, migration, and invasion of breast cancer cells. Br J Cancer. 2009;101:38–47.

Bonaccorsi L, Marchiani S, Muratori M, Forti G, Baldi E. Gefitinib (‘IRESSA’, ZD1839) inhibits EGF-induced invasion in prostate cancer cells by suppressing PI3 K/AKT activation. J Cancer Res Clin Oncol. 2004;130:604–14.

Parker JJ, Dionne KR, Massarwa R, et al. Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma. Neuro Oncol. 2013;15:1048–57.

Ono M, Hirata A, Kometani T, et al. Sensitivity to gefitinib (Iressa, ZD1839) in non-small cell lung cancer cell lines correlates with dependence on the epidermal growth factor (EGF) receptor/extracellular signal-regulated kinase 1/2 and EGF receptor/Akt pathway for proliferation. Mol Cancer Ther. 2004;3:465–72.

Ceppi P, Papotti M, Monica V, et al. Effects of Src kinase inhibition induced by dasatinib in non-small cell lung cancer cell lines treated with cisplatin. Mol Cancer Ther. 2009;8:3066–74.

Song L, Morris M, Bagui T, Lee FY, Jove R, Haura EB. Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival. Cancer Res. 2006;66:5542–8.

Logue JS, Morrison DK. Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. Genes Dev. 2012;26:641–50.

Chong CR, Janne PA. The quest to overcome resistance to EGFR-targeted therapies in cancer. Nat Med. 2013;19:1389–400.

von Manstein V, Yang CM, Richter D, Delis N, Vafaizadeh V, Groner B. Resistance of Cancer Cells to Targeted Therapies Through the Activation of Compensating Signaling Loops. Curr Signal Transduct Ther. 2013;8:193–202.

O’Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66:1500–8.

Picaud L, Thibault B, Mery E, et al. Evaluation of the effects of hyaluronic acid-carboxymethyl cellulose barrier on ovarian tumor progression. J Ovarian Res. 2014;7:40.

Ward BG, Wallace K, Shepherd JH, Balkwill FR. Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice. Cancer Res. 1987;47:2662–7.

Shaw TJ, Senterman MK, Dawson K, Crane CA, Vanderhyden BC. Characterization of intraperitoneal, orthotopic, and metastatic xenograft models of human ovarian cancer. Mol Ther. 2004;10:1032–42.