Skip to main content
SpringerLink
Log in

Clinical Relevance of Targeted Interference with Src-Mediated Signal Transduction Events

  • Chapter
Targeted Interference with Signal Transduction Events

Part of the book series: Resent Results in Cancer Research ((RECENTCANCER,volume 172))

Abstract

In the past decade, we have gained substantial insight into various signal transduction and molecular pathways regulating cancer cells. Moreover, we have recently been able to develop specific targeted therapies instead of classic chemotherapeutics that attempt to essentially provide more toxicity to the tumor than the normal cell. As a result, we have been able to decrease adverse side effects, thus improving the quality of life of cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aberle H, Butz S, Stappert J, Weissig H, Kemler R, Hoschuetzky H (1994) Assembly of the cadherincatenin complex in vitro with recombinant proteins. J Cell Sci 107:3655–3663

    PubMed  CAS  Google Scholar 

  • Akhand AA, Pu M, Senga T, Kato M, Suzuki H, Miyata T, Hamaguchi M, Nakashima I (1999) Nitric oxide controls src kinase activity through a sulfhydryl group modification-mediated Tyr-527-independent and Tyr-416-linked mechanism. J Biol Chem 274:25821–25826

    Article  PubMed  CAS  Google Scholar 

  • Angers-Loustau A, Hering R, Werbowetski TE, Kaplan DR, Del Maestro RF (2004) SRC regulates actin dynamics and invasion of malignant glial cells in three dimensions. Mol Cancer Res 2:595–605

    PubMed  CAS  Google Scholar 

  • Aronin N (2006) Target selectivity in mRNA silencing. Gene Ther 13:509–516

    Article  PubMed  CAS  Google Scholar 

  • Bijlmakers MJ, and Marsh M (2000) Hsp90 is essential for the synthesis and subsequent membrane association, but not the maintenance, of the Src-kinase p56(lck). Mol Biol Cell 11:1585–1595

    PubMed  CAS  Google Scholar 

  • Blake RA, Broome MA, Liu X, Wu J, Gishizky M, Sun L, Courtneidge SA (2000) SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol 20:9018–9027

    Article  PubMed  CAS  Google Scholar 

  • Boschelli DH, Ye F, Wang YD, Dutia M, Johnson SL, Wu B, Miller K, Powell DW, Yaczko D, Young M, Tischler M, Arndt K, Discafani C, Etienne C, Gibbons J, Grod J, Lucas J, Weber JM, Boschelli F (2001) Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J Med Chem 44:3965–3977

    Article  PubMed  CAS  Google Scholar 

  • Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R (2001) Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci USA 98:7319–7324

    Article  PubMed  CAS  Google Scholar 

  • Boyce BF, Yoneda T, Lowe C, Soriano P, Mundy GR (1992) Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J Clin Invest 90:1622–1627

    PubMed  CAS  Google Scholar 

  • Boyer B, Bourgeois Y, Poupon MF (2002) Src kinase contributes to the metastatic spread of carcinoma cells. Oncogene 21:2347–2356

    Article  PubMed  CAS  Google Scholar 

  • Cam WR, Masaki T, Shiratori Y, Kato N, Ikenoue T, Okamoto M, Igarashi K, Sano T, Omata M (2001) Reduced C-terminal Src kinase activity is correlated inversely with pp60(c-src) activity in colorectal carcinoma. Cancer 92:61–70

    Article  PubMed  CAS  Google Scholar 

  • Chen T, George JA, Taylor CC (2006) Src tyrosine kinase as a chemotherapeutic target: is there a clinical case? Anticancer Drugs 17:123–131

    Article  PubMed  Google Scholar 

  • Chen YT, Stewart DB, Nelson WJ (1999) Coupling assembly of the E-cadherin/beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells. J Cell Biol 144:687–699

    Article  PubMed  CAS  Google Scholar 

  • Chen Z, Lee FY, Bhalla KN, Wu J (2006) Potent inhibition of platelet-derived growth factor-induced responses in vascular smooth muscle cells by BMS-354825. Mol Pharmacol

    Google Scholar 

  • Contri A, Brunati AM, Trentin L, Cabrelle A, Miorin M, Cesaro L, Pinna LA, Zambello R, Semenzato G, Donella-Deana A (2005) Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis. J Clin Invest 115:369–378

    Article  PubMed  CAS  Google Scholar 

  • Cross FR, Garber EA, Hanafusa H (1985) N-terminal deletions in Rous sarcoma virus p60src:effects on tyrosine kinase and biological activities and on recombination in tissue culture with the cellular src gene. Mol Cell Biol 5:2789–2795

    PubMed  CAS  Google Scholar 

  • Crowe DL, Tsang KJ, Shemirani B (2001) Jun N-terminal kinase 1 mediates transcriptional induction of matrix metalloproteinase 9 expression. Neoplasia 3:27–32

    Article  PubMed  CAS  Google Scholar 

  • Cullen B R (2005) Does RNA interference have a future as a treatment for HIV-1 induced disease? AIDS Rev 7:22–25

    PubMed  Google Scholar 

  • Dalgarno D, Stehle T, Narula S, Schelling P, van Schravendijk MR, Adams S, Andrade L, Keats J, Ram M, Jin L, Grossman T, MacNeil I, Metcalf C 3rd, Shakespeare W, Wang Y, Keenan T, Sundaramoorthi R, Bohacek R, Weigele M, Sawyer T (2006) Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds. Chem Biol Drug Des 67:46–57

    Article  PubMed  CAS  Google Scholar 

  • Doggrell SA (2005) BMS-354825:a novel drug with potential for the treatment of imatinib-resistant chronic myeloid leukaemia. Expert Opin Investig Drugs 14:89–91

    Article  PubMed  Google Scholar 

  • Duxbury MS, Ito H, Zinner MJ, Ashley SW, and Whang EE (2004) siRNA directed against c-Src enhances pancreatic adenocarcinoma cell gemcitabine chemosensitivity. J Am Coll Surg 198:953–959

    Article  PubMed  Google Scholar 

  • Eastell R, Hannon RA, Gallagher NJ, Clack G, Macpherson M, Marshall AL (2005) The effect of AZD0530, a highly selective, orally available Src/Abl kinase inhibitor, on biomarkers of bone resorption in healthy males. American Society of Clinical Oncology, Orlando, FL

    Google Scholar 

  • Erlichman C, Toft D, Reid J, Goetz M, Ames M, Mandrekar S, Ajei A, McCollum A, Ivy P (2004) A phase I trial of 17-allylamino-geldanamycin (17AAG) in patients with advanced cancer. American Society of Clinical Oncology, New Orleans, LA

    Google Scholar 

  • Evans TR, Morgan JA, van den Abbeele AD, McPherson IR, George S, Crawford D, Mastrullo M, Cheng S, Fletcher JA, and Demetri GD (2005) Phase I doseescalation study of the Src and multi-kinase inhibitor BMS-354825 in patients (pts) with GIST and other solid tumors. American Society of Clinical Oncology, Orlando, FL

    Google Scholar 

  • Fujisawa K, Madaule P, Ishizaki T, Watanabe G, Bito H, Saito Y, Hall A, Narumiya S (1998) Different regions of Rho determine Rho-selective binding of different classes of Rho target molecules. J Biol Chem 273:18943–18949

    Article  PubMed  CAS  Google Scholar 

  • Glaze ER, Lambert AL, Smith AC, Page JG, Johnson WD, McCormick DL, Brown AP, Levine BS, Covey JM, Egorin MJ, Eiseman JL, Holleran JL, Sausville EA, and Tomaszewski JE (2005) Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs:potential clinical relevance. Cancer Chemother Pharmacol 56:637–647

    Article  PubMed  CAS  Google Scholar 

  • Golas JM, Arndt K, Etienne C, Lucas J, Nardin D, Gibbons J, Frost P, Ye F, Boschelli DH, Boschelli F (2003) SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res 63:375–381

    PubMed  CAS  Google Scholar 

  • Gururajan M, Chui R, Karuppannan AK, Ke J, Jennings CD, Bondada S (2005) c-Jun N-terminal kinase (JNK) is required for survival and proliferation of B-lymphoma cells. Blood 106:1382–1391

    Article  PubMed  CAS  Google Scholar 

  • Hakak Y, Martin GS (1999) Ubiquitin-dependent degradation of active Src. Curr Biol 9:1039–1042

    Article  PubMed  CAS  Google Scholar 

  • Hartson SD, Matts RL (1994) Association of Hsp90 with cellular Src-family kinases in a cell-free system correlates with altered kinase structure and function. Biochemistry 33:8912–8920

    Article  PubMed  CAS  Google Scholar 

  • He H, Hirokawa Y, Levitzki A, and Maruta H (2000) An anti-Ras cancer potential of PP1, an inhibitor specific for Src family kinases: in vitro and in vivo studies. Cancer J 6:243–248

    PubMed  CAS  Google Scholar 

  • Helgason CD, Damen JE, Rosten P, Grewal R, Sorensen P, Chappel SM, Borowski A, Jirik F, Krystal G, Humphries RK (1998) Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span. Genes Dev 12:1610–1620

    PubMed  CAS  Google Scholar 

  • Hennequin LF, Allen J, Costello G, Fennell M, Green TP, Jacobs V, Morgentin R, Olivier A, Ple PA (2005) The discovery of AZD0530:a novel, oral, highly selective and dual-specific inhibitor of the Src and Abl family kinases. Proc Am Assoc Cancer Res 46:A2537

    Google Scholar 

  • Herynk MH, Beyer A, Cui Y, Green TP, Fuqua SAW (2005) c-Src inhibition with AZD0530 reduces estrogen mediated growth and invasion in breast cancer cells expressing the K303R ERα mutant. Proc Am Assoc Cancer Res 46:A264

    Google Scholar 

  • Hideshima T, Bradner JE, Wong J, Chauhan D, Richardson P, Schreiber SL, and Anderson KC (2005) Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci USA 102:8567–8572

    Article  PubMed  CAS  Google Scholar 

  • Hiscox S, Barrow D, Green T, Nicholson RI (2005) Adhesion-independent focal adhesion kinase activation involves Src and promotes cell adhesion and motility in tamoxifen-resistant MCF-7 cells and is inhibited by the Src/Abl kinase inhibitor AZD0530. Proc Am Assoc Cancer Res 46:A266

    Google Scholar 

  • Hsia DA, Mitra SK, Hauck CR, Streblow DN, Nelson JA, Ilic D, Huang S, Li E, Nemerow GR, Leng J, Spencer KS, Cheresh DA, Schlaepfer DD (2003) Differential regulation of cell motility and invasion by FAK. J Cell Biol 160:753–767

    Article  PubMed  CAS  Google Scholar 

  • Hu Y, Liu Y, Pelletier S, Buchdunger E, Warmuth M, Fabbro D, Hallek M, Van Etten RA, Li S (2004) Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet 36:453–461

    Article  PubMed  CAS  Google Scholar 

  • Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69:11–25

    Article  PubMed  CAS  Google Scholar 

  • Imai K, Loewenstein A, Koroma B, Grebe R, de Juan E Jr (2000) Herbimycin A in the treatment of experimental proliferative vitreoretinopathy: toxicity and efficacy study. Graefes Arch Clin Exp Ophthalmol 238:440–447

    Article  PubMed  CAS  Google Scholar 

  • Irby R, Mao W, Coppola D, Jove R, Gamero A, Cuthbertson D, Fujita D, Yeatman TJ (1997) Overexpression of normal c-Src in poorly metastatic human colon cancer cells enhances primary tumor growth but not metastatic potential. Cell Growth Differ 8:1287–1295

    PubMed  CAS  Google Scholar 

  • Jones RJ, Avizienyte E, Wyke AW, Owens DW, Brunton VG, Frame MC (2002) Elevated c-Src is linked to altered cell-matrix adhesion rather than proliferation in KM12C human colorectal cancer cells. Br J Cancer 87:1128–1135

    Article  PubMed  CAS  Google Scholar 

  • Karni R, Mizrachi S, Reiss-Sklan E, Gazit A, Livnah O, Levitzki A (2003) The pp60c-Src inhibitor PP1 is noncompetitive against ATP. FEBS Lett 537:47–52

    Article  PubMed  CAS  Google Scholar 

  • Kilarski WW, Jura N, Gerwins P (2003) Inactivation of Src family kinases inhibits angiogenesis in vivo: implications for a mechanism involving organization of the actin cytoskeleton. Exp Cell Res 291:70–82

    Article  PubMed  CAS  Google Scholar 

  • Kim M, Tezuka T, Tanaka K, Yamamoto T (2004) Cblc suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Oncogene 23:1645–1655

    Article  PubMed  CAS  Google Scholar 

  • Laird AD, Li G, Moss KG, Blake RA, Broome MA, Cherrington JM, Mendel DB (2003) Src family kinase activity is required for signal tranducer and activator of transcription 3 and focal adhesion kinase phosphorylation and vascular endothelial growth factor signaling in vivo and for anchorage-dependent and-independent growth of human tumor cells. Mol Cancer Ther 2:461–469

    PubMed  CAS  Google Scholar 

  • Lauffenburger DA Horwitz AF (1996) Cell migration: a physically integrated molecular process. Cell 84:359–369

    Article  PubMed  CAS  Google Scholar 

  • Laukaitis CM, Webb DJ, Donais K, Horwitz AF (2001) Differential dynamics of alpha 5 integrin, paxillin, and alpha-actinin during formation and disassembly of adhesions in migrating cells. J Cell Biol 153:1427–1440

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Bishop A, Witucki L, Kraybill B, Shimizu E, Tsien J, Ubersax J, Blethrow J, Morgan DO, Shokat KM (1999) Structural basis for selective inhibition of Src family kinases by PP1. Chem Biol 6:671–678

    Article  PubMed  CAS  Google Scholar 

  • Lockton JA, Smethurst D, Macpherson M, Tootell R, Marshall AL, Clack G, Gallagher NJ (2005) Phase I ascending single and multiple dose studies to assess the safety, tolerability and pharmacokinetics of AZD0530, a highly selective, dual-specific Src-Abl inhibitor. American Society of Clinical Oncology, Orlando, FL

    Google Scholar 

  • Logie A, Martin PD, Partridge EA, Byatt SL, Whittaker RD, Green TP (2005) Pharmacokinetics, tissue distribution and anti-tumor activity of the Src/Abl kinase inhibitor AZD0530 in rat xenograft model. Proc Am Assoc Cancer Res 43:A5989

    Google Scholar 

  • Longworth MS, Laimins LA (2006) Histone deacetylase 3 localizes to the plasma membrane and is a substrate of Src. Oncogene

    Google Scholar 

  • Lopez-Maderuelo MD, Fernandez-Renart M, Moratilla C, Renart J (2001) Opposite effects of the Hsp90 inhibitor Geldanamycin: induction of apoptosis in PC12, and differentiation in N2A cells. FEBS Lett 490:23–27

    Article  PubMed  CAS  Google Scholar 

  • Mao W, Irby R, Coppola D, Fu L, Wloch M, Turner J, Yu H, Garcia R, Jove R, Yeatman TJ (1997) Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. Oncogene 15:3083–3090

    Article  PubMed  CAS  Google Scholar 

  • Martin GS (2004) The road to Src. Oncogene 23:7910–7917

    Article  PubMed  CAS  Google Scholar 

  • Masaki T, Okada M, Tokuda M, Shiratori Y, Hatase O, Shirai M, Nishioka M, Omata M (1999) Reduced Cterminal Src kinase (Csk) activities in hepatocellular carcinoma. Hepatology 29:379–384

    Article  PubMed  CAS  Google Scholar 

  • Masamune A, Satoh M, Kikuta K, Suzuki N, Shimosegawa T (2005) Activation of JAK-STAT pathway is required for platelet-derived growth factor-induced proliferation of pancreatic stellate cells. World J Gastroenterol 11:3385–3391

    PubMed  CAS  Google Scholar 

  • McCollum GW, Rajaratnam VS, Bullard LE, Yang R, Penn JS (2004) Herbimycin A inhibits angiogenic activity in endothelial cells and reduces neovascularization in a rat model of retinopathy of prematurity. Exp Eye Res 78:987–995

    Article  PubMed  CAS  Google Scholar 

  • Missbach M, Jeschke M, Feyen J, Muller K, Glatt M, Green J, Susa M (1999) A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone 24:437–449

    Article  PubMed  CAS  Google Scholar 

  • Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N (1999) Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res 59:6145–6152

    PubMed  CAS  Google Scholar 

  • Montgomery MK, Xu S, Fire A (1998) RNA as a target of double-stranded RNA-mediated genetic interference in Caenorhabditis elegans. Proc Natl Acad Sci USA 95:15502–15507

    Article  PubMed  CAS  Google Scholar 

  • Mullender MG, Everts V, Green TP, Klein-Nulend J (2005) Inhibition of osteoclastic bone resorption by the novel, potent, and selective c-Src/Abl kinase inhibitor, AZD0530. Proc Am Assoc Cancer Res 46:A2923

    Google Scholar 

  • Nakagawa T, Tanaka S, Suzuki H, Takayanagi H, Miyazaki T, Nakamura K, Tsuruo T (2000) Overexpression of the csk gene suppresses tumor metastasis in vivo. Int J Cancer 88:384–391

    Article  PubMed  CAS  Google Scholar 

  • Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J, Zhang S, Wang T, Sinibaldi D, Coppola D, Heller R, Ellis LM, Karras J, Bromberg J, Pardoll D, Jove R, Yu H (2002) Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21:2000–2008

    Article  PubMed  CAS  Google Scholar 

  • O’Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, Metcalf CA 3rd, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK, Deininger MW, Druker BJ (2004) Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor:implications for CML. Blood 104:2532–2539

    Article  PubMed  CAS  Google Scholar 

  • Okabe M, Uehara Y, Noshima T, Itaya T, Kunieda Y, Kurosawa M (1994) In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABLtransfected cells. Leuk Res 18:867–873

    Article  PubMed  CAS  Google Scholar 

  • Oneyama C, Agatsuma T, Kanda Y, Nakano H, Sharma SV, Nakano S, Narazaki F, Tatsuta K (2003) Synthetic inhibitors of proline-rich ligand-mediated proteinprotein interaction:potent analogs of UCS15A. Chem Biol 10:443–451

    Article  PubMed  CAS  Google Scholar 

  • Oneyama C, Nakano H, Sharma SV (2002) UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug. Oncogene 21:2037–2050

    Article  PubMed  CAS  Google Scholar 

  • Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G (1998) A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392:190–193

    Article  PubMed  CAS  Google Scholar 

  • Ple PA, Green TP, Hennequin LF, Curwen J, Fennell M, Allen J, Lambert-Van Der Brempt C, Costello G (2004) Discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of c-Src. J Med Chem 47:871–887

    Article  PubMed  CAS  Google Scholar 

  • Ptasznik A, Nakata Y, Kalota A, Emerson SG, and Gewirtz AM (2004) Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells. Nat Med 10:1187–1189

    Article  PubMed  CAS  Google Scholar 

  • Randall G, Grakoui A, Rice CM (2003) Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs. Proc Natl Acad Sci USA 100:235–240

    Article  PubMed  CAS  Google Scholar 

  • Recchia I, Rucci N, Funari A, Migliaccio S, Taranta A, Longo M, Kneissel M, Susa M, Fabbro D, Teti A (2004) Reduction of c-Src activity by substituted 5,7-diphenyl-pyrrolo[2,3-d]-pyrimidines induces osteoclast apoptosis in vivo and in vitro. Involvement of ERK1/2 pathway. Bone 34:65–79

    Article  PubMed  CAS  Google Scholar 

  • Rubin H (1955) Quantitative relations between causative virus and cell in the Rous no. 1 chicken sarcoma. Virology 1:445–73

    Article  PubMed  CAS  Google Scholar 

  • Sawyer T, Shakespeare W, Wang Y, Metcalf CA 3rd, Sundaramoorthi R, Keenan T, Bohacek R, Dalgarno D, Xing L, and Boyce B (2003) A new class of small-molecule therapeutics for osteolytic bone metastasis:discovery of novel bone-targeted Src tyrosine kinase inhibitors having potent in vitro and in vivo activities. American Society of Clinical Oncology, Chicago, IL

    Google Scholar 

  • Sawyers CL, Shah NP, Kantarjian HM, Cortes J, Paquette R, Nicoll J, Bai SA, Clark E, Decillis AP, Talpaz M (2005) A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant accelerated and blast phase chronic myeloid leukemia (CML): results from CA 180002. American Society of Clinical Oncology, Orlando, FL

    Google Scholar 

  • Shah NP, Lee FY, Luo R, Jiang Y, Donker M, Akin C (2006) Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in the majority of patients with systemic mastocytosis. Blood

    Google Scholar 

  • Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL (2004) Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305:399–401

    Article  PubMed  CAS  Google Scholar 

  • Shakespeare W, Yang M, Bohacek R, Cerasoli F, Stebbins K, Sundaramoorthi R, Azimioara M, Vu C, Pradeepan S, Metcalf C 3rd, Haraldson C, Merry T, Dalgarno D, Narula S, Hatada M, Lu X, van Schravendijk MR, Adams S, Violette S, Smith J, Guan W, Bartlett C, Herson J, Iuliucci J, Weigele M, T Sawyer (2000) Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity. Proc Natl Acad Sci USA 97:9373–9378

    Article  PubMed  CAS  Google Scholar 

  • Sharma SV, Oneyama C, Yamashita Y, Nakano H, Sugawara K, Hamada M, Kosaka N, Tamaoki T (2001) UCS15A, a non-kinase inhibitor of Src signal transduction. Oncogene 20:2068–2079

    Article  PubMed  CAS  Google Scholar 

  • Soriano P, Montgomery C, Geske R, Bradley A (1991) Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64:693–702

    Article  PubMed  CAS  Google Scholar 

  • Summy JM, Trevino JG, Lesslie DP, Baker CH, Shakespeare WC, Wang Y, Sundaramoorthi R, Metcalf CA 3rd, Keats JA, Sawyer TK, Gallick GE (2005) AP23846, a novel and highly potent Src family kinase inhibitor, reduces vascular endothelial growth factor and interleukin-8 expression in human solid tumor cell lines and abrogates downstream angiogenic processes. Mol Cancer Ther 4:1900–1911

    Article  PubMed  CAS  Google Scholar 

  • Takeshita S, Namba N, Zhao JJ, Jiang Y, Genant HK, Silva MJ, Brodt MD, Helgason CD, Kalesnikoff J, Rauh MJ, Humphries RK, Krystal G, Teitelbaum SL, Ross FP (2002) SHIP-deficient mice are severely osteoporotic due to increased numbers of hyper-resorptive osteoclasts. Nat Med 8:943–949

    Article  PubMed  CAS  Google Scholar 

  • Talpaz M, Kantarjian HM, Paquette R, Shah NP, Cortes J, Nicoll J, Bai SA, Huang F, Decillis AP, Sawyers CL (2005) A phase I study of BMS-354825 in patients with imatinib-resistant and intolerant chronic phase chronic myeloid leukemia (CML): results from CA180002. American Society of Clinical Oncology, Orlando, FL

    Google Scholar 

  • Termuhlen PM, Curley SA, Talamonti MS, Saboorian MH, Gallick GE (1993) Site-specific differences in pp60c-src activity in human colorectal metastases. J Surg Res 54:293–298

    Article  PubMed  CAS  Google Scholar 

  • Tice DA, Biscardi JS, Nickles AL, Parsons SJ (1999) Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci U S A 96:1415–1420

    Article  PubMed  CAS  Google Scholar 

  • Timpson P, Jones GE, Frame MC, Brunton VG (2001) Coordination of cell polarization and migration by the Rho family GTPases requires Src tyrosine kinase activity. Curr Biol 11:1836–1846

    Article  PubMed  CAS  Google Scholar 

  • Vaucheret H, Kronenberger J, Lepingle A, Vilaine F, Boutin JP, Caboche M (1992) Inhibition of tobacco nitrite reductase activity by expression of antisense RNA. Plant J 2:559–569

    PubMed  CAS  Google Scholar 

  • Wang Y, Metcalf CA 3rd, Shakespeare WC, Sundaramoorthi R, Keenan TP, Bohacek RS, van Schravendijk MR, Violette SM, Narula SS, Dalgarno DC, Haraldson C, Keats J, Liou S, Mani U, Pradeepan S, Ram M, Adams S, Weigele M, Sawyer TK (2003) Bone-targeted 2,6,9-trisubstituted purines:novel inhibitors of Src tyrosine kinase for the treatment of bone diseases. Bioorg Med Chem Lett 13:3067–3070

    Article  PubMed  CAS  Google Scholar 

  • Warmuth M, Simon N, Mitina O, Mathes R, Fabbro D, Manley PW, Buchdunger E, Forster K, Moarefi I, Hallek M (2003) Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate-resistant Bcr-Abl kinases. Blood 101:664–672

    Article  PubMed  CAS  Google Scholar 

  • Weis S, Shintani S, Weber A, Kirchmair R, Wood M, Cravens A, McSharry H, Iwakura A, Yoon YS, Himes N, Burstein D, Doukas J, Soll R, Losordo D, Cheresh D (2004) Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J Clin Invest 113:885–894

    Article  PubMed  CAS  Google Scholar 

  • Wisniewski D, Lambek CL, Liu C, Strife A, Veach DR, Nagar B, Young MA, Schindler T, Bornmann WG, Bertino JR, Kuriyan J, Clarkson B (2002) Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases. Cancer Res 62:4244–4255

    PubMed  CAS  Google Scholar 

  • Yang L, Kowalski JR, Zhan X, Thomas SM, Luscinskas FW (2006) Endothelial cell cortactin phosphorylation by Src contributes to polymorphonuclear leukocyte transmigration in vitro. Circ Res 98:394–402

    Article  PubMed  CAS  Google Scholar 

  • Yang WM, Tsai SC, Wen YD, Fejer G, Seto E (2002) Functional domains of histone deacetylase-3. J Biol Chem 277:9447–9454

    Article  PubMed  CAS  Google Scholar 

  • Yeatman TJ (2004) A renaissance for SRC. Nat Rev Cancer 4:470–480

    Article  PubMed  CAS  Google Scholar 

  • Yezhelyev MV, Koehl G, Guba M, Brabletz T, Jauch KW, Ryan A, Barge A, Green T, Fennell M, Bruns CJ (2004) Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res 10:8028–8036

    Article  PubMed  CAS  Google Scholar 

  • Yu CL, Meyer DJ, Campbell GS, Larner AC, Carter-Su C, Schwartz J, Jove R (1995) Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269:81–83

    Article  PubMed  CAS  Google Scholar 

  • Yu H, Jove R (2004) The STATs of cancer-new molecular targets come of age. Nat Rev Cancer 4:97–105

    Article  PubMed  CAS  Google Scholar 

  • Zamir E, Geiger B (2001) Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 114:3583–3590

    PubMed  CAS  Google Scholar 

  • Zhang Q, Fairchild RL, Reich MB, Miller GG (2005) Inhibition of Src kinases combined with CD40 ligand blockade prolongs murine cardiac allograft survival. Transplantation 80:1112–1120

    Article  PubMed  CAS  Google Scholar 

  • Zhao WQ, Alkon DL, Ma W (2003) c-Src protein tyrosine kinase activity is required for muscarinic receptor-mediated DNA synthesis and neurogenesis via ERK1/2 and c-AMP-responsive element-binding protein signaling in neural precursor cells. J Neurosci Res 72:334–342

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Quan P. Ly MD (Assistant Professor of Surgery) & Timothy J. Yeatman MD (Professor of Surgery)

Authors
  1. Quan P. Ly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy J. Yeatman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Georg-Speyer-Haus, Institute for Biomedical Research, Paul-Ehrlich-Str. 42-44, 60596, Frankfurt am Main, Germany

    Bernd Groner (Director) (Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Ly, Q.P., Yeatman, T.J. (2007). Clinical Relevance of Targeted Interference with Src-Mediated Signal Transduction Events. In: Groner, B. (eds) Targeted Interference with Signal Transduction Events. Resent Results in Cancer Research, vol 172. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-31209-3_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-31209-3_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-31208-6

  • Online ISBN: 978-3-540-31209-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation