Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs.

[1]  Marc-André Elsliger,et al.  Rare cancer-specific mutations in PIK3CA show gain of function , 2007, Proceedings of the National Academy of Sciences.

[2]  A. Iafrate,et al.  Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling , 2007, Proceedings of the National Academy of Sciences.

[3]  Rakesh K. Jain,et al.  PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma and Attenuates the Response to Anti-VEGF Treatment , 2009, PloS one.

[4]  M. Koch,et al.  Tumor Escape from Endogenous, Extracellular Matrix–Associated Angiogenesis Inhibitors by Up-Regulation of Multiple Proangiogenic Factors , 2008, Clinical Cancer Research.

[5]  J. D. de Bono,et al.  Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu). , 2007, European journal of cancer.

[6]  Syam B Nair,et al.  A novel multi-target drug screening strategy directed against key proteins of DAPk family. , 2013, Combinatorial chemistry & high throughput screening.

[7]  J. S. Gutkind,et al.  Epidermal growth factor receptor-independent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system. , 2003, Cancer research.

[8]  M. Socinski,et al.  A single-arm phase II trial of pazopanib in patients with advanced non-small cell lung cancer with non-squamous histology with disease progression on bevacizumab containing therapy. , 2014, Lung cancer.

[9]  V. V. Kleandrova,et al.  Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents. , 2012, Bioorganic & medicinal chemistry.

[10]  Jane Fridlyand,et al.  Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors , 2012, Nature.

[11]  Feng Xu,et al.  Therapeutic target database update 2014: a resource for targeted therapeutics , 2013, Nucleic Acids Res..

[12]  S. Agarwal,et al.  Association of constitutively activated hepatocyte growth factor receptor (Met) with resistance to a dual EGFR/Her2 inhibitor in non-small-cell lung cancer cells , 2009, British Journal of Cancer.

[13]  Jun Yu,et al.  Cyclooxygenase-2 in tumorigenesis of gastrointestinal cancers: an update on the molecular mechanisms. , 2010, Cancer letters.

[14]  F. Peale,et al.  VEGF‐null cells require PDGFR α signaling‐mediated stromal fibroblast recruitment for tumorigenesis , 2004, The EMBO journal.

[15]  J. Litz,et al.  The multi-targeted kinase inhibitor SU5416 inhibits small cell lung cancer growth and angiogenesis, in part by blocking Kit-mediated VEGF expression. , 2004, Lung cancer.

[16]  J. Engelman,et al.  The Role of the ErbB Family Members in Non–Small Cell Lung Cancers Sensitive to Epidermal Growth Factor Receptor Kinase Inhibitors , 2006, Clinical Cancer Research.

[17]  O. Kallioniemi,et al.  Mammary-Derived Growth Inhibitor Alters Traffic of EGFR and Induces a Novel Form of Cetuximab Resistance , 2009, Clinical Cancer Research.

[18]  J. Blay,et al.  Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial , 2012, The Lancet.

[19]  A. Citri,et al.  EGF–ERBB signalling: towards the systems level , 2006, Nature Reviews Molecular Cell Biology.

[20]  Yan Sun,et al.  Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. , 2012, The Lancet. Oncology.

[21]  Jorge S Reis-Filho,et al.  Genetic heterogeneity and cancer drug resistance. , 2012, The Lancet. Oncology.

[22]  Yuzong Chen,et al.  Exploration of acridine scaffold as a potentially interesting scaffold for discovering novel multi-target VEGFR-2 and Src kinase inhibitors. , 2011, Bioorganic & medicinal chemistry.

[23]  Yuzong Chen,et al.  Discovery of benzimidazole derivatives as novel multi-target EGFR, VEGFR-2 and PDGFR kinase inhibitors. , 2011, Bioorganic & medicinal chemistry.

[24]  M. P. Freitas,et al.  aug-MIA-QSAR modeling of antimicrobial activities and design of multi-target anilide derivatives. , 2013, Journal of microbiological methods.

[25]  Andreas Zell,et al.  Inferring multi-target QSAR models with taxonomy-based multi-task learning , 2013, Journal of Cheminformatics.

[26]  P. Vogt,et al.  Cancer-specific mutations in PIK3CA are oncogenic in vivo , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Y. Ichinose,et al.  LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  M. Meyerson,et al.  BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models , 2008, Oncogene.

[29]  Barbara Sennino,et al.  Controlling escape from angiogenesis inhibitors , 2012, Nature Reviews Cancer.

[30]  Chun-song Zheng,et al.  Network pharmacology-based prediction of the multi-target capabilities of the compounds in Taohong Siwu decoction, and their application in osteoarthritis , 2013, Experimental and therapeutic medicine.

[31]  Rodrigo Dienstmann,et al.  Drug development to overcome resistance to EGFR inhibitors in lung and colorectal cancer , 2012, Molecular oncology.

[32]  M. Karamouzis,et al.  Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR inhibitors. , 2009, The Lancet. Oncology.

[33]  Yang Song,et al.  Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery , 2011, Nucleic Acids Res..

[34]  Tiejun Li,et al.  Development of RNA interference-based therapeutics and application of multi-target small interfering RNAs. , 2014, Nucleic acid therapeutics.

[35]  S. Johansson,et al.  EGFR and beta1 integrins utilize different signaling pathways to activate Akt. , 2008, Experimental cell research.

[36]  Ming-Chih Crouthamel,et al.  Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity , 2007, Molecular Cancer Therapeutics.

[37]  Jeffrey W. Clark,et al.  Lessons from phase III clinical trials on anti-VEGF therapy for cancer , 2006, Nature Clinical Practice Oncology.

[38]  A. Joe,et al.  Mechanisms of Disease: oncogene addiction—a rationale for molecular targeting in cancer therapy , 2006, Nature Clinical Practice Oncology.

[39]  G. Toyokawa,et al.  Updated Evidence on the Mechanisms of Resistance to ALK Inhibitors and Strategies to Overcome Such Resistance: Clinical and Preclinical Data , 2015, Oncology Research and Treatment.

[40]  M. Nöthen,et al.  A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer , 2012, Nature Medicine.

[41]  Joon-Oh Park,et al.  MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling , 2007, Science.

[42]  K. Shokat,et al.  Escape from HER family tyrosine kinase inhibitor therapy by the kinase inactive HER3 , 2007, Nature.

[43]  V V Poroikov,et al.  PASS Targets: Ligand-based multi-target computational system based on a public data and naïve Bayes approach$ , 2015, SAR and QSAR in environmental research.

[44]  M. Kris,et al.  Phase II Study of the Multitargeted Tyrosine Kinase Inhibitor XL647 in Patients with Non–Small-Cell Lung Cancer , 2012, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[45]  Boon Chuan Low,et al.  In-Silico Approaches to Multi-target Drug Discovery , 2010, Pharmaceutical Research.

[46]  M. Gottesman,et al.  Targeting multidrug resistance in cancer , 2006, Nature Reviews Drug Discovery.

[47]  M. Schlumberger,et al.  A Phase II Trial of the Multitargeted Tyrosine Kinase Inhibitor Lenvatinib (E7080) in Advanced Medullary Thyroid Cancer , 2015, Clinical Cancer Research.

[48]  Monilola A. Olayioye,et al.  The ErbB signaling network: receptor heterodimerization in development and cancer , 2000, The EMBO journal.

[49]  P. Bunn,et al.  A new generation of EGFR tyrosine-kinase inhibitors in NSCLC. , 2012, The Lancet. Oncology.

[50]  Alexander Kamb,et al.  Why is cancer drug discovery so difficult? , 2007, Nature Reviews Drug Discovery.

[51]  D. Haber,et al.  Cancer: Drivers and passengers , 2007, Nature.

[52]  Jinan Wang,et al.  System-level multi-target drug discovery from natural products with applications to cardiovascular diseases , 2014, Molecular Diversity.

[53]  R. Brezinschek,et al.  Mutation analysis of the PTEN/MMAC1 gene in lung cancer , 1998, Oncogene.

[54]  J. Sun,et al.  EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers , 2011, Nature Medicine.

[55]  P. Jänne,et al.  Combined Vascular Endothelial Growth Factor Receptor and Epidermal Growth Factor Receptor (EGFR) Blockade Inhibits Tumor Growth in Xenograft Models of EGFR Inhibitor Resistance , 2009, Clinical Cancer Research.

[56]  D. Yee,et al.  Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. , 2008, The Journal of clinical investigation.

[57]  Lin Tao,et al.  Clustered patterns of species origins of nature-derived drugs and clues for future bioprospecting , 2011, Proceedings of the National Academy of Sciences.

[58]  P. Johnston,et al.  Cancer drug resistance: an evolving paradigm , 2013, Nature Reviews Cancer.

[59]  C. Sawyers,et al.  Cancer: Mixing cocktails , 2007, Nature.

[60]  Feng Luan,et al.  Unified multi-target approach for the rational in silico design of anti-bladder cancer agents. , 2013, Anti-cancer agents in medicinal chemistry.

[61]  Péter Csermely,et al.  The efficiency of multi-target drugs: the network approach might help drug design. , 2004, Trends in pharmacological sciences.

[62]  Stuart Thomson,et al.  Kinase switching in mesenchymal-like non-small cell lung cancer lines contributes to EGFR inhibitor resistance through pathway redundancy , 2008, Clinical & Experimental Metastasis.

[63]  Feng Liu,et al.  Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors. , 2011, European journal of medicinal chemistry.

[64]  A. Ullrich,et al.  Cell communication networks: epidermal growth factor receptor transactivation as the paradigm for interreceptor signal transmission , 2001, Oncogene.

[65]  Y Z Chen,et al.  Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries. , 2012, Journal of molecular graphics & modelling.

[66]  Ian Walker,et al.  Do molecularly targeted agents in oncology have reduced attrition rates? , 2009, Nature Reviews Drug Discovery.

[67]  M. Meyerson,et al.  The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP , 2008, Proceedings of the National Academy of Sciences.

[68]  Daniel A. Haber,et al.  Epidermal growth factor receptor mutations in lung cancer , 2007, Nature Reviews Cancer.

[69]  Edward S. Kim,et al.  Implication of the Insulin-like Growth Factor-IR Pathway in the Resistance of Non–small Cell Lung Cancer Cells to Treatment with Gefitinib , 2007, Clinical Cancer Research.

[70]  J. Bos,et al.  The ras gene family and human carcinogenesis. , 1988, Mutation research.

[71]  David B Solit,et al.  Resistance to MEK Inhibitors: Should We Co-Target Upstream? , 2011, Science Signaling.

[72]  V. Patel,et al.  Epidermal Growth Factor Receptor-independent Constitutive Activation of STAT 3 in Head and Neck Squamous Cell Carcinoma Is Mediated by the Autocrine / Paracrine Stimulation of the Interleukin 6 / gp 130 Cytokine System , 2003 .

[73]  Zhe Shi,et al.  Computer Aided Multi-target Drug Design, Multi-target Virtual Screening , 2010 .

[74]  Peter J. Parker,et al.  HER2 Oncogenic Function Escapes EGFR Tyrosine Kinase Inhibitors via Activation of Alternative HER Receptors in Breast Cancer Cells , 2008, PloS one.

[75]  Chun-Ming Tsai,et al.  Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.