Synergistic combinations of signaling pathway inhibitors: Mechanisms for improved cancer therapy

Adams, 2007, Rapid turnover of mcl-1 couples translation to cell survival and apoptosis, J. Biol. Chem., 282, 6192, 10.1074/jbc.M610643200 Anjum, 2008, The RSK family of kinases: emerging roles in cellular signalling, Nat. Rev. Mol. Cell Biol., 9, 747, 10.1038/nrm2509 Antonescu, 2008, Targeted therapies in gastrointestinal stromal tumors, Semin. Diagn. Pathol., 25, 295, 10.1053/j.semdp.2008.08.004 Arteaga, 2007, HER3 and mutant EGFR meet MET, Nat. Med., 13, 675, 10.1038/nm0607-675 Azzariti, 2008, Synergic antiproliferative and antiangiogenic effects of EGFR and mTOR inhibitors on pancreatic cancer cells, Biochem. Pharmacol., 75, 1035, 10.1016/j.bcp.2007.11.018 Baradari, 2007, Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells, World J. Gastroenterol., 13, 4458, 10.3748/wjg.v13.i33.4458 Bean, 2007, MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib, Proc. Natl. Acad. Sci. U.S.A., 104, 20932, 10.1073/pnas.0710370104 Bedogni, 2006, Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase kinase 1/2 prevents melanoma development and promotes melanoma regression in the transgenic TPRas mouse model, Mol. Cancer Ther., 5, 3071, 10.1158/1535-7163.MCT-06-0269 Benavente, 2009, Establishment and characterization of a model of acquired resistance to epidermal growth factor receptor targeting agents in human cancer cells, Clin. Cancer Res., 15, 1585, 10.1158/1078-0432.CCR-08-2068 Broxterman, 2005, Anticancer therapeutics: “Addictive” targets, multi-targeted drugs, new drug combinations, Drug Resist. Updates, 8, 183, 10.1016/j.drup.2005.07.002 Canduri, 2008, CDK9 a potential target for drug development, Med. Chem., 4, 210, 10.2174/157340608784325205 Carnero, 2008, The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications, Curr. Cancer Drug Targets, 8, 187, 10.2174/156800908784293659 Carracedo, 2008, Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer, J. Clin. Invest., 118, 3065 Carter, 1998, Inhibition of the mitogen activated protein (MAP) kinase cascade potentiates cell killing by low dose ionizing radiation in A431 human squamous carcinoma cells, Oncogene, 16, 2787, 10.1038/sj.onc.1201802 Chu, 2009, Mechanisms of resistance to FLT3 inhibitors, Drug Resist. Updates, 12, 8, 10.1016/j.drup.2008.12.001 Cragg, 2007, Gefitinib-induced killing of NSCLC cell lines expressing mutant EGFR requires BIM and can be enhanced by BH3 mimetics, PLoS Med., 4, 1681, 10.1371/journal.pmed.0040316 Dai, 2008, Interruption of the Ras/MEK/ERK signaling cascade enhances Chk1 inhibitor-induced DNA damage in vitro and in vivo in human multiple myeloma cells, Blood, 112, 2439, 10.1182/blood-2008-05-159392 Dai, 2002, Combined treatment with the checkpoint abrogator UCN-01 and MEK1/2 inhibitors potently induces apoptosis in drug-sensitive and -resistant myeloma cells through an IL-6-independent mechanism, Blood, 100, 3333, 10.1182/blood-2002-03-0940 Dasmahapatra, 2007, Synergistic interactions between vorinostat and sorafenib in chronic myelogenous leukemia cells involve Mcl-1 and p21CIP1 down-regulation, Clin. Cancer Res., 13, 4280, 10.1158/1078-0432.CCR-07-0835 Deng, 2007, Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion, Cancer Res., 67, 11867, 10.1158/0008-5472.CAN-07-1961 Dent, 2003, MAPK pathways in radiation responses, Oncogene, 22, 5885, 10.1038/sj.onc.1206701 Di Cosimo, 2008, Targeted therapies in breast cancer: where are we now?, Eur. J. Cancer, 44, 2781, 10.1016/j.ejca.2008.09.026 Druker, 2008, Translation of the Philadelphia chromosome into therapy for CML, Blood, 112, 4808, 10.1182/blood-2008-07-077958 Engelman, 2008, Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers, Nat. Med., 14, 1351, 10.1038/nm.1890 Emanuele, 2008, Histone deacetylase inhibitors: apoptotic effects and clinical implications, Int. J. Oncol., 33, 637 Fan, 2007, A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma, Cancer Res., 67, 7960, 10.1158/0008-5472.CAN-07-2154 Fleming, 2008, Synergistic inhibition of ErbB signaling by combined treatment with seliciclib and ErbB-targeting agents, Clin. Cancer Res., 14, 4326, 10.1158/1078-0432.CCR-07-4633 Fornier, 2007, Phase I dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors, Clin. Cancer Res., 13, 5841, 10.1158/1078-0432.CCR-07-1218 Frost, 2009, Regulation of D-cyclin translation inhibition in myeloma cells treated with mammalian target of rapamycin inhibitors: rationale for combined treatment with extracellular signal-regulated kinase inhibitors and rapamycin, Mol. Cancer Ther., 8, 83, 10.1158/1535-7163.MCT-08-0254 Festuccia, 2008, Akt down-modulation induces apoptosis of human prostate cancer cells and synergizes with EGFR tyrosine kinase inhibitors, Prostate, 68, 965, 10.1002/pros.20757 Gahr, 2008, The histone-deacetylase inhibitor MS-275 and the CDK-inhibitor CYC-202 promote anti-tumor effects in hepatoma cell lines, Oncol. Rep., 20, 1249 Gao, 2004, Contribution of disruption of the nuclear factor-kappaB pathway to induction of apoptosis in human leukemia cells by histone deacetylase inhibitors and flavopiridol, Mol. Pharmacol., 66, 956, 10.1124/mol.104.002014 Gonzalez, 2008, Combination therapy for malignant glioma based on PTEN status, Expert Rev. Anticancer Ther., 8, 1767, 10.1586/14737140.8.11.1767 Grant, 2007, Simultaneous interruption of signal transduction and cell cycle regulatory pathways: implications for new approaches to the treatment of childhood leukemias, Curr. Drug Targets, 8, 751, 10.2174/138945007780830764 Grant, 2008, Cotargeting survival signaling pathways in cancer, J. Clin. Invest., 118, 3003, 10.1172/JCI36898E1 Grant, 2008, Is the focus moving toward a combination of targeted drugs?, Best Pract. Res. Clin. Haematol., 21, 629, 10.1016/j.beha.2008.08.003 Haass, 2008, The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel, Clin. Cancer Res., 14, 230, 10.1158/1078-0432.CCR-07-1440 Hamed, 2008, Transient exposure of carcinoma cells to RAS/MEK inhibitors and UCN-01 causes cell death in vitro and in vivo, Mol. Cancer Ther., 7, 616, 10.1158/1535-7163.MCT-07-2376 Harari, 2007, Biology of interactions: antiepidermal growth factor receptor agents, J. Clin. Oncol., 25, 4057, 10.1200/JCO.2007.11.8984 Hida, 2009, Gefitinib for the treatment of non-small-cell lung cancer, Expert Rev. Anticancer Ther., 9, 17, 10.1586/14737140.9.1.17 Howes, 2007, The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures, Mol. Cancer Ther., 6, 2505, 10.1158/1535-7163.MCT-06-0698 Huang, 2009, The mechanisms of differential sensitivity to an insulin-like growth factor-1 receptor inhibitor (BMS-536924) and rationale for combining with EGFR/HER2 inhibitors, Cancer Res., 69, 161, 10.1158/0008-5472.CAN-08-0835 Huston, 2008, Targeting Akt and heat shock protein 90 produces synergistic multiple myeloma cell cytotoxicity in the bone marrow microenvironment, Clin. Cancer Res., 14, 865, 10.1158/1078-0432.CCR-07-1299 Ihle, 2009, Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy, Mol. Cancer Ther., 8, 1, 10.1158/1535-7163.MCT-08-0801 Ihle, 2009, Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance, Cancer Res., 69, 143, 10.1158/0008-5472.CAN-07-6656 Ihle, 2005, The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts, Mol. Cancer Ther., 4, 1349, 10.1158/1535-7163.MCT-05-0149 Janmaat, 2006, Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cells, Int. J. Cancer, 118, 209, 10.1002/ijc.21290 Jasinghe, 2008, ABT-869, a multi-targeted tyrosine kinase inhibitor, in combination with rapamycin is effective for subcutaneous hepatocellular carcinoma xenograft, J. Hepatol., 49, 985, 10.1016/j.jhep.2008.08.010 Jiang, 2008, Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment, Drug Resist. Updates, 11, 63, 10.1016/j.drup.2008.03.001 Jimeno, 2007, Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacy, Br. J. Cancer, 96, 952, 10.1038/sj.bjc.6603656 Jin, 2008, Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer, J. Mammary Gland Biol. Neoplasia, 13, 485, 10.1007/s10911-008-9107-3 Jänne, 2006, Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors, Clin Cancer Res., 12, 4416s, 10.1158/1078-0432.CCR-06-0555 Kinkade, 2008, Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model, J. Clin. Invest., 118, 3051 Knobbe, 2008, The roles of PTEN in development, physiology and tumorigenesis in mouse models: a tissue-by-tissue survey, Oncogene, 27, 5398, 10.1038/onc.2008.238 Koliopanos, 2008, Molecular aspects of carcinogenesis in pancreatic cancer, Hepatobil. Pancreat. Dis. Int., 7, 345 Kroog, 2008, Systemic therapy for metastatic renal cell carcinoma, Urol. Clin. N. Am., 35, 687, 10.1016/j.ucl.2008.07.007 Ladanyi, 2008, Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond, Mod. Pathol., 21, S16, 10.1038/modpathol.3801018 Lasithiotakis, 2008, Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells, J. Invest. Dermatol., 128, 2013, 10.1038/jid.2008.44 Lee, 2003, BAY-43-9006 Bayer/Onyx, Curr. Opin. Invest. Drugs, 4, 757 Le Tourneau, 2008, Progress and challenges in the identification of biomarkers for EGFR and VEGFR targeting anticancer agents, Drug Resist. Updates, 11, 99, 10.1016/j.drup.2008.04.001 Loeffler-Ragg, 2008, EGFR inhibition as a therapy for head and neck squamous cell carcinoma, Expert Opin. Invest. Drugs, 17, 1517, 10.1517/13543784.17.10.1517 LoPiccolo, 2008, Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations, Drug Resist. Updates, 11, 32, 10.1016/j.drup.2007.11.003 Martin, 2008, Lapatinib resistance in HCT116 cells is mediated by elevated MCL-1 expression and decreased BAK activation and not by ERBB receptor kinase mutation, Mol. Pharmacol., 74, 807, 10.1124/mol.108.047365 Martin, 2007, The farnesyltransferase inhibitor R115777 (tipifarnib) in combination with tamoxifen acts synergistically to inhibit MCF-7 breast cancer cell proliferation and cell cycle progression in vitro and in vivo, Mol. Cancer Ther., 6, 2458, 10.1158/1535-7163.MCT-06-0452 McConkey, 2008, Mechanisms of proteasome inhibitor action and resistance in cancer, Drug Resist. Updates, 11, 164, 10.1016/j.drup.2008.08.002 McCubrey, 2008, Targeting the Raf/MEK/ERK pathway with small-molecule inhibitors, Curr. Opin. Invest. Drugs, 9, 614 McKinstry, 2002, Inhibitors of MEK1/2 interact with UCN-01 to induce apoptosis and reduce colony formation in mammary and prostate carcinoma cells, Cancer Biol. Ther., 1, 243, 10.4161/cbt.75 Memmott, 2009, Akt-dependent and independent mechanisms of mTOR regulation in cancer, Cell Signal., 21, 178, 10.1016/j.cellsig.2009.01.004 Mitchell, 2007, Extrinsic pathway- and cathepsin-dependent induction of mitochondrial dysfunction are essential for synergistic flavopiridol and vorinostat lethality in breast cancer cells, Mol. Cancer Ther., 6, 3101, 10.1158/1535-7163.MCT-07-0561 Moghul, 1994, Modulation of c-MET proto-oncogene (HGF receptor) mRNA abundance by cytokines and hormones: evidence for rapid decay of the 8kb c-MET transcript, Oncogene, 9, 2045 Mohapatra, 2009, Apoptosis of metastatic prostate cancer cells by a combination of cyclin-dependent kinase and AKT inhibitors, Int. J. Biochem. Cell Biol., 41, 595, 10.1016/j.biocel.2008.07.013 Mueller, 2008, Met and c-Src cooperate to compensate for loss of epidermal growth factor receptor kinase activity in breast cancer cells, Cancer Res., 68, 3314, 10.1158/0008-5472.CAN-08-0132 Nguyen, 2006, Synergistic interactions between DMAG and mitogen-activated protein kinase kinase 1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib mesylate, Clin. Cancer Res., 12, 2239, 10.1158/1078-0432.CCR-05-2282 O’Reilly, 2006, mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt, Cancer Res., 66, 1500, 10.1158/0008-5472.CAN-05-2925 Pao, 2004, EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib, Proc. Natl. Acad. Sci. U.S.A., 101, 13306, 10.1073/pnas.0405220101 Park, 2008, Mitogen-activated protein kinase kinase 1/2 inhibitors and 17-allylamino-17-demethoxy geldanamycin synergize to kill human gastrointestinal tumor cells in vitro via suppression of c-FLIP-s levels and activation of CD95, Mol. Cancer Ther., 7, 2633, 10.1158/1535-7163.MCT-08-0400 Park, 2008, Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation, Cancer Biol. Ther., 7, 1648, 10.4161/cbt.7.10.6623 Pei, 2007, MEK1/2 inhibitors potentiate UCN-01 lethality in human multiple myeloma cells through a Bim-dependent mechanism, Blood, 110, 2092, 10.1182/blood-2007-04-083204 Phelps, 2009, Clinical response and pharmacokinetics from a phase I study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia, Blood, 10.1182/blood-2008-07-168583 Rahmani, 2005, Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation, J. Biol. Chem., 280, 35217, 10.1074/jbc.M506551200 Rahmani, 2007, The kinase inhibitor sorafenib induces cell death through a process involving induction of endoplasmic reticulum stress, Mol. Cell. Biol., 27, 5499, 10.1128/MCB.01080-06 Raman, 2007, Differential regulation and properties of MAPKs, Oncogene, 26, 3100, 10.1038/sj.onc.1210392 Ramos, 2008, The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells, Int. J. Biochem. Cell Biol., 40, 2707, 10.1016/j.biocel.2008.04.009 Reinehr, 2003, Bile salt-induced hepatocyte apoptosis involves epidermal growth factor receptor-dependent CD95 tyrosine phosphorylation, Gastroenterology, 125, 839, 10.1016/S0016-5085(03)01055-2 Rengan, 2008, Clinical target promiscuity: lessons from ras molecular trials, Cancer Metastasis Rev., 27, 403, 10.1007/s10555-008-9133-z Ryan, 2008, FDA drug approval summary: lapatinib in combination with capecitabine for previously treated metastatic breast cancer that overexpresses HER-2, Oncologist, 13, 1114, 10.1634/theoncologist.2008-0816 Sartore-Bianchi, 2009, PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies, Cancer Res., 69, 1851, 10.1158/0008-5472.CAN-08-2466 Sebolt-Leopold, 2004, Targeting the mitogen-activated protein kinase cascade to treat cancer, Nat. Rev. Cancer, 4, 937, 10.1038/nrc1503 Senderowicz, 1999, Flavopiridol: the first cyclin-dependent kinase inhibitor in human clinical trials, Invest. New Drugs, 17, 313, 10.1023/A:1006353008903 Shapiro, 2004, Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol, Clin. Cancer Res., 10, 4270s, 10.1158/1078-0432.CCR-040020 Sizemore, 1999, Pharmacological inhibition of Ras-transformed epithelial cell growth is linked to down-regulation of epidermal growth factor-related peptides, Gastroenterology, 117, 567, 10.1016/S0016-5085(99)70449-X Smalley, 2008, Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas, Mol. Cancer Ther., 7, 2876, 10.1158/1535-7163.MCT-08-0431 Smalley, 2006, Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases, Mol. Cancer Ther., 5, 1136, 10.1158/1535-7163.MCT-06-0084 Stahl, 2004, Deregulated Akt3 activity promotes development of malignant melanoma, Cancer Res., 64, 7002, 10.1158/0008-5472.CAN-04-1399 Sordella, 2004, Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways, Science, 305, 1163, 10.1126/science.1101637 Steelman, 2008, Akt as a therapeutic target in cancer, Expert Opin. Ther. Targets, 12, 1139, 10.1517/14728222.12.9.1139 Sturgill, 2008, MAP kinase: it's been longer than fifteen minutes, Biochem. Biophys. Res. Commun., 371, 1, 10.1016/j.bbrc.2008.04.002 Takada, 2004, Flavopiridol inhibits NF-κB activation induced by various carcinogens and inflammatory agents through inhibition of IκBα kinase and p65 phosphorylation: abrogation of cyclin D1, cyclooxygenase-2, and matrix metalloprotease-9, J. Biol. Chem., 279, 4750, 10.1074/jbc.M304546200 Takigawa, 2007, Combination of SN-38 with gefitinib or imatinib overcomes SN-38-resistant small-cell lung cancer cells, Oncol. Rep., 17, 983 Takimoto, 2008, Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials, Cancer Chemother. Pharmacol., 61, 535, 10.1007/s00280-007-0639-9 Tímár, 2008, Antiangiogenic drugs and tyrosine kinases, Anticancer Agents Med. Chem., 8, 462, 10.2174/187152008784533035 Tochizawa, 2008, Antitumor effects of a combination of interferon-alpha and sorafenib on human renal carcinoma cell lines, Biomed. Res., 29, 271, 10.2220/biomedres.29.271 Tol, 2009, Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer, N. Engl. J. Med., 360, 563, 10.1056/NEJMoa0808268 Tsai, 2008, Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity, Proc. Natl. Acad. Sci. U.S.A., 105, 3041, 10.1073/pnas.0711741105 Valerie, 2007, Radiation-induced cell signaling: inside-out and outside-in, Mol. Cancer Ther., 6, 789, 10.1158/1535-7163.MCT-06-0596 Wang, 2008, Overcoming mTOR inhibition-induced paradoxical activation of survival signaling pathways enhances mTOR inhibitors’ anticancer efficacy, Cancer Biol. Ther., 7, 1952, 10.4161/cbt.7.12.6944 Wang, 2008, Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma, Clin. Cancer Res., 14, 5124, 10.1158/1078-0432.CCR-07-4774 Wesierska-Gadek, 2007, Inhibition of farnesyl protein transferase sensitizes human MCF-7 breast cancer cells to roscovitine-mediated cell cycle arrest, J. Cell. Biochem., 102, 736, 10.1002/jcb.21325 Wong, 2009, Recent developments in anti-cancer agents targeting the Ras/Raf/MEK/ERK pathway, Recent Pat. Anticancer Drug Discov., 4, 28, 10.2174/157489209787002461 Yacoub, 2006, Radiotherapy-induced signal transduction, Endocr. Relat. Cancer, 13, S99, 10.1677/erc.1.01271 Yacoub, 2006, MEK1/2 inhibition promotes taxotere lethality in mammary tumors in vivo, Cancer Biol. Ther., 5, 1332, 10.4161/cbt.5.10.3215 Yacoub, 2003, Melanoma differentiation-associated 7 (interleukin 24) inhibits growth and enhances radiosensitivity of glioma cells in vitro and in vivo, Clin. Cancer Res., 9, 3272 Yu, 2003, The lethal effects of pharmacological cyclin-dependent kinase inhibitors in human leukemia cells proceed through a phosphatidylinositol 3-kinase/Akt-dependent process, Cancer Res., 63, 1822 Zhang, 2008, Vorinostat and sorafenib synergistically kill tumor cells via FLIP suppression and CD95 activation, Clin. Cancer Res., 14, 5385, 10.1158/1078-0432.CCR-08-0469 Zhao, 2008, Class I PI3K in oncogenic cellular transformation, Oncogene, 27, 5486, 10.1038/onc.2008.244