Current status of Src inhibitors in solid tumor malignancies

Oncologist

Volumn 16, Issue 5, 2011, Pages 566-578

  Puls, Lauren N ^a   Eadens, Matthew ^b   Messersmith, Wells ^a  

^a UNIVERSITY OF COLORADO CANCER CENTER   (United States)

^b MAYO CLINIC   (United States)

Author keywords

Biologic; Bosutinib; Dasatinib; Saracatinib; Solid tumor; Src inhibitors

Indexed keywords

ANASTROZOLE; B RAF KINASE; BOSUTINIB; CAPECITABINE; CARBOPLATIN; CETUXIMAB; DASATINIB; DCC 2036; ERLOTINIB; EXEMESTANE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IMATINIB; KX 2 391; LETROZOLE; OXALIPLATIN; PACLITAXEL; PLACEBO; PONATINIB; PROTEIN SRC; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR; SARACATINIB; STEM CELL FACTOR RECEPTOR; TG 100435; TG 100855; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; XL 228;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANEMIA; ANOREXIA; ARTHRALGIA; BONE MARROW SUPPRESSION; BREAST CANCER; CARCINOGENESIS; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); COLON CANCER; DIARRHEA; DISEASE MARKER; DRUG TARGETING; ENZYME STRUCTURE; FATIGUE; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; HEADACHE; HEMATOLOGIC MALIGNANCY; HUMAN; KIDNEY FAILURE; LEUKEMIA; LEUKOPENIA; LUNG NON SMALL CELL CANCER; LYMPHOMA; MELANOMA; MESOTHELIOMA; METASTASIS; MYALGIA; NAUSEA; NEUTROPENIA; ONCOGENE; OVARY CANCER; PANCREAS CANCER; PANCREATITIS; PANCYTOPENIA; PLEURA EFFUSION; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN FUNCTION; RASH; REVIEW; SALIVARY GLAND CANCER; SARCOMA; SIDE EFFECT; SOLID TUMOR; SRC GENE; STOMACH CANCER; THROMBOCYTOPENIA; VOMITING;

ANILINE COMPOUNDS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BENZODIOXOLES; CLINICAL TRIALS AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; NEOPLASMS; NITRILES; PROTEIN KINASE INHIBITORS; PYRIMIDINES; QUINAZOLINES; QUINOLINES; SRC-FAMILY KINASES; THIAZOLES;

EID: 79956283619     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2010-0408     Document Type: Review

References (100)

1. Rous P. A sarcoma of the fowl transmissible by an agent separable from the tumors cells. J Exp Med 1911;13:397-411.
2. Rubin H. Quantitative relations between causative virus and cell in the Rous no. 1 chicken sarcoma. Virology 1955;1:445-473.
3. Martin GS. Rous sarcoma virus: A function required for the maintenance of the transformed state. Nature 1970;227:1021-1023.
4. Stehelin D, Varmus HE, Bishop JM et al. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 1976;260:170-173.
5. Stehelin D, Guntaka RV, Varmus HE et al. Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J Mol Biol 1976;101:349-365.
6. Martin GS. The road to Src. Oncogene 2004;23:7910-7917.
7. Yeatman TJ. A renaissance for Src. Nat Rev Cancer 2004;4:470-480.
8. Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol 1997;13:513-609.
9. Bolen JB, Brugge JS. Leukocyte protein tyrosine kinases: Potential targets for drug discovery. Annu Rev Immunol 1997;15:371-404.
10. Roskoski R Jr. Src protein-tyrosine kinase structure and regulation. Biochem Biophys Res Commun 2004;324:1155-1164.
11. Manning G, Whyte DB, Martinez R et al. The protein kinase complement of the human genome. Science 2002;298:1912-1934.
12. Haskell MD, Slack JK, Parsons JT et al. c-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes. Chem Rev 2001;101:2425-2440.
13. Brown MT, Cooper JA. Regulation, substrates, and functions of Src. Biochim Biophys Acta 1996;1287:121-149.
14. Fujita Y, Krause G, Scheffner M et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol 2002;4:222-231.
15. Zamir E, Geiger B. Molecular complexity and dynamics of cell-matrix adhesions. J Cell Sci 2001;114:3583-3590.
16. Noritake H, Miyamori H, Goto C et al. Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in metastatic MDCK cells transformed by v-Src. Clin Exp Metastasis 1999;17:105-110.
17. Hsia DA, Mitra SK, Hauck CR et al. Differential regulation of cell motility and invasion by FAK. J Cell Biol 2003;160:753-767.
18. Niu G, Wright KL, Huang M et al. Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 2002;21:2000-2008.
19. Parsons JT, Parsons SJ. Src family protein tyrosine kinases: Cooperating with growth factor and adhesion signaling pathways. Curr Opin Cell Biol 1997;9:187-192.
20. Courtneidge S, Fumagalli S, Koegl M et al. The Src family of protein tyrosine kinases: Regulation and functions. Dev Suppl 1993:57-64.
21. LaVallee TM, Prudovsky IA, McMahon GA et al. Activation of the MAP kinase pathway by FGF-1 correlates with cell proliferation induction while activation of the Src pathway correlates with migration. J Cell Biol 1998;141:1647-1658.
22. Levitzki A. Src as a target for anti-cancer drugs. Anticancer Drug Des 1996;11:175-182.
23. Luttrell DK, Lee A, Lansing TJ et al. Involvement of pp60c-Src with two major signaling pathways in human breast cancer. Proc Natl Acad Sci U S A 1994;91:83-87.
24. Rahimi N, Hung W, Tremblay E et al. c-Src kinase activity is required for hepatocyte growth factor-induced motility and anchorage-independent growth of mammary carcinoma cells. J Biol Chem 1998;273:33714-33721.
25. Tice DA, Biscardi JS, Nickles AL et al. Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc Natl Acad Sci U S A 1999;96:1415-1420.
26. Peterson JE, Kulik G, Jelinek T et al. Src phosphorylates the insulin-like growth factor type I receptor on the autophosphorylation sites. Requirement for transformation by Src. J Biol Chem 1996;271:31562-31571.
27. Alvarez RH, Kantarjian HM, Cortes JE. The role of Src in solid and hematologic malignancies: Development of new-generation Src inhibitors. Cancer 2006;107:1918-1929.
28. Mao W, Irby R, Coppolla D et al. Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. Oncogene 1997;15:3083-3090.
29. Maa MC, Leu TH, McCarley DJ et al. Potentiation of epidermal growth factor receptor-mediated oncogenesis by c-Src: Implications for the etiology of multiple human cancers. Proc Natl Acad Sci U S A 1995;92:6981-1985.
30. Xing C, Imagawa W. Altered MAP kinase (ERK1,2) regulation in primary cultures of mammary tumor cells: Elevated basal activity and sustained response to EGF. Carcinogenesis 1999;20:1201-1208.
31. Salh B, Marotta A, Matthewson C et al. Investigation of the Meh-MAP kinase-Rsk pathway in human breast cancer. Anticancer Res 1999;19: 731-740.
32. Summy JM, Gallick GE. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev 2003;22:337-358.
33. Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene 2000;19:5636-5642.
34. Bolen JB, Veillette A, Schwartz AM et al. Analysis of pp60c-Src in human colon carcinoma and normal human colon mucosal cells. Oncogene Res 1987;1:149-168.
35. Talamonti MS, Roh MS, Curley SA et al. Increase in activity and level of pp60c-Src in progressive stages of human colorectal cancer. J Clin Invest 1993;91:53-60.
36. Park J, Meisler AI, Cartwright CA. c-Yes tyrosine kinase activity in human colon carcinoma. Oncogene 1993;8:2627-2635.
37. Cattan N, Rochet N, Mazeau C et al. Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scattering and epithelial to mesenchyme transition induced by growth factors. Br J Cancer 2001;85:1412-1417.
38. Kumble S, Omary MB, Cartwright CA et al. Src activation in malignant and premalignant epithelia of Barrett's esophagus. Gastroenterology 1997;112:348-356.
39. Jankowski J, Coghill G, Hopwood D et al. Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus. Gut 1992;33:1033-1038.
40. Mazurenko NN, Kogan EA, Zborovskaya IB et al. Expression of pp60c-Src in human small cell and non-small cell lung carcinomas. Eur J Cancer 1992;28:372-377.
41. Rosen N, Bolen JB, Schwartz AM et al. Analysis of pp60c-Src protein kinase activity in human tumor cell lines and tissues. J Biol Chem 1986; 261:13754-13759.
42. Jacobs C, Rubsamen H. Expression of pp60c-Src protein kinase in adult and fetal human tissue: High activities in some sarcomas and mammary carcinomas. Cancer Res 1983;43:1696-1702.
43. Tan M, Li P, Klos KS et al. ErbB2 promotes Src synthesis and stability: Novel mechanisms of Src activation that confer breast cancer metastasis. Cancer Res 2005;65:1858-1867.
44. Lutz MP, Esser IB, Flossmann-Kast BB et al. Overexpression and activation of the tyrosine kinase Src in human pancreatic carcinoma. Biochem Biophys Res Commun 1998;243:503-508.
45. Rajeshkumar NV, Tan AC, De Oliveira E et al. Antitumor effects and biomarkers of activity of AZD0530, a Src inhibitor, in pancreatic cancer. Clin Cancer Res 2009;15:4138-4146.
46. Messersmith WA, Rajeshkumar NV, Tan AC et al. Efficacy and pharmacodynamic effects of bosutinib (SKI-606), a Src/Abl inhibitor, in freshly generated human pancreas cancer xenografts. Mol Cancer Ther 2009;8: 1484-1493.
47. Flossmann-Kast BB, Jehle PM, Hoeflich A et al. Src stimulates insulinlike growth factor I (IGF-I)-dependent cell proliferation by increasing IGF-I receptor number in human pancreatic carcinoma cells. Cancer Res 1998;58:3551-3554.
48. Kantarjian H, Shah NP, Hochhaus A et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-2270.
49. 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;67:2800-2808.
50. Nam S, Kim D, Cheng JQ et al. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer Res 2005;65:9185-9189.
51. 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;5:3014-3022.
52. Johnson FM, Saigal B, Talpaz M et al. 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;11:6924-6932.
53. Tsao AS, He D, Saigal B et al. Inhibition of c-Src expression and activation in malignant pleural mesothelioma tissues leads to apoptosis, cell cycle arrest, and decreased migration and invasion. Mol Cancer Ther 2007; 6:1962-1972.
54. Song L, Morris M, Bagui T et al. Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival. Cancer Res 2006;66:5542-5548.
55. Tryfonopoulos D, O'Donovan N, Corkery B et al. Activity of dasatinib with chemotherapy in triple-negative breast cancer cells. J Clin Oncol 2009;27(15 suppl):Abstract e14605.
56. 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;67:2226-2238.
57. Trevino JG, Summy JM, Lesslie DP et al. Inhibition of Src expression and activity inhibits tumor progression and metastasis of human pancreatic adenocarcinoma cells in an orthotopic nude mouse model. Am J Pathol 2006;168:962-972.
58. Eustace AJ, Crown J, Clynes M et al. Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines. J Transl Med 2008;6: 53.
59. Demetri GD, Lo Russo P, MacPherson IR et al. Phase I dose-escalation and pharmacokinetic study of dasatinib in patients with advanced solid tumors. Clin Cancer Res 2009;15:6232-6240.
60. Haura EB, Tanvetyanon T, Chiappori A et al. Phase I/II study of the Src inhibitor dasatinib in combination with erlotinib in advanced non-smallcell lung cancer. J Clin Oncol 2010;28:1387-1394.
61. Lieu CH, Wolff RA, Eng C. Phase IB study of the Src inhibitor dasatinib with FOLFOX and cetuximab in metastatic colorectal cancer. J Clin Oncol 2010;28(15 suppl):Abstract 3536.
62. Yu EY, Wilding G, Posadas E et al. Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res 2009; 15:7421-7428.
63. Araujo J, Armstrong A, Braud EL et al. Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086). J Clin Oncol 2009;27(15 suppl): Abstract 5061.
64. Mayer E, Baurain J, Sparano J et al. Dasatinib in advanced HER2/neu amplified and ER/PR-positive breast cancer: Phase II study CA180088. J Clin Oncol 2009;27(15 suppl):Abstract 1011.
65. Algazi AP, Weber JS, Andrews S et al. A phase I/II trial of DTIC and dasatinib in metastatic melanoma. J Clin Oncol 2010;28(15 suppl):Abstract 8532.
66. Johnson FM, Bekele BN, Feng L et al. Phase II study of dasatinib in patients with advanced non-small-cell lung cancer. J Clin Oncol 2010;28: 4609-4615.
67. Hiscox S, Morgan L, Green TP et al. Elevated Src activity promotes cellular invasion and motility in tamoxifen resistant breast cancer cells. Breast Cancer Res Treat 2006;97:263-274.
68. Chang YM, Bai L, Liu S et al. Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530. Oncogene 2008;27: 6365-6375.
69. Purnell PR, Mack PC, Tepper CG et al. The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells. J Thorac Oncol 2009;4:448-454.
70. Koppikar P, Choi SH, Egloff AM et al. Combined inhibition of c-Src and epidermal growth factor receptor abrogates growth and invasion of head and neck squamous cell carcinoma. Clin Cancer Res 2008;14:4284-4291.
71. Nowak D, Boehrer S, Hochmuth S et al. Src kinase inhibitors induce apoptosis and mediate cell cycle arrest in lymphoma cells. Anticancer Drugs 2007;18:981-995.
72. Arcaroli JJ, Touban BM, Tan AC et al. Gene array and fluorescence in situ hybridization biomarkers of activity of saracatinib (AZD0530), a Src inhibitor, in a preclinical model of colorectal cancer. Clin Cancer Res 2010; 16:4165-4177.
73. Green TP, Fennell M, Whittaker R et al. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol 2009;3:248-261.
74. Baselga J, Cervantes A, Martinelli E et al. Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. Clin Cancer Res 2010;16:4876-4883.
75. Renouf DJ, Moore MJ, Hedley D et al. A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer. Invest New Drugs 2010 Dec 18 [Epub ahead of print].
76. Fury MG, Baxi S, Shen R et al. Phase II study of saracatinib (AZD0530) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Anticancer Res 2011;31:249-253.
77. Mackay HJ, Au HJ, McWhirter E et al. A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: A trial of the PMH phase II consortium. Invest New Drugs 2011 Mar 12 [Epub ahead of print].
78. Lara PN Jr, Longmate J, Evans CP et al. A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: A California Cancer Consortium study. Anticancer Drugs 2009; 20:179-184.
79. Gajewski T, Zha Y, Clark J. Phase II study of the Src family kinase inhibitor saracatinib (AZD0530) in metastatic melanoma. J Clin Oncol 2010; 28(15 suppl):Abstract 8562.
80. Messersmith WA, Nallapareddy S, Arcaroli J et al. A phase II trial of saracatinib (AZD0530), an oral Src inhibitor, in previously treated metastatic pancreatic cancer. J Clin Oncol 2010;28(suppl):Abstract e14515.
81. Traina TA, Sparano JA, Caravelli J et al. Phase II trial of saracatinib in patients (pts) with ER/PR-negative metastatic breast cancer (MBC). J Clin Oncol 2010;28(15 suppl):Abstract 1086.
82. Poole C, Lisyanskaya A, Rodenhuis S et al. Arandomized phase II clinical trial of the Src inhibitor saracatinib (AZD0530) with carboplatin + paclitaxel vs. placebo, carboplatin+paclitaxel in patients with recurrent platinum-sensitive epithelial ovarian cancer. Ann Oncol 2010;21(suppl 8): 9720.
83. Jallal H, Valentino ML, Chen G et al. A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo. Cancer Res 2007;67:1580-1588.
84. 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 beta-catenin and its nuclear signaling. Cancer Res 2006;66:2279-2286.
85. 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: 5358-5364.
86. Messersmith WA, Krishnamurthi S, Hewes BA et al. Bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor: Preliminary results from a phase 1 study in patients with advanced malignant solid tumors. J Clin Oncol 2007;25(18 suppl):Abstract 3552.
87. + ALL. J Clin Oncol 2008;26(suppl):Abstract 7049.
88. Bruemmendorf TH, Cervantes F, Kim D et al. Bosutinib is safe and active in patients with chronic phase CML with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. J Clin Oncol 2008;26(suppl): Abstract 7001.
89. Adjei AA, Cohen R, Kurzrock R et al. Results of a phase I trial of KX2-391, a novel non-ATP competitive substrate-pocket directed SRC inhibitor, in patients with advanced malignancies. J Clin Oncol 2009;27(15 suppl):Abstract 3511.
90. Cortes J, Talpaz M, Bixby D et al. A phase 1 trial of oral ponatinib (AP24534) in patients with refractory chronic myelogenous leukemia (CML) and other hematologic malignancies: Emerging safety and clinical response findings. Presented at the American Society of Hematology 2010 Annual Meeting.
91. Schweppe RE, Kerege AA, French JD et al. Inhibition of Src with AZD0530 reveals the Src-Focal Adhesion kinase complex as a novel therapeutic target in papillary and anaplastic thyroid cancer. J Clin Endocrinol Metab 2009;94:2199-2203.
92. Moulder S, Yan K, Huang F et al. Development of candidate genomic markers to select breast cancer patients for dasatinib therapy. Mol Cancer Ther 2010;9:1120-1127.
93. Mendiratta P, Mostaghel E, Guinney J et al. Genomic strategy for targeting therapy in castration-resistant prostate cancer. J Clin Oncol 2009;27: 2022-2029.
94. Morris PG, Chang JC, Abbruzzi A et al. Correlative biomarkers in a phase II study of dasatinib (D) and weekly (w) paclitaxel (P) for patients (Pts) with metastatic breast carcinoma (MBC). J Clin Oncol 2010;28(15 suppl): Abstract TPS124.
95. Lu-Emerson C, Norden AD, Drappatz J et al. Retrospective study of dasatinib in recurrent high-grade glioma (HGG) patients who failed bevacizumab. J Clin Oncol 2010;28(suppl):Abstract e12525.
96. Johnson FM, Agrawal S, Burris H et al. Phase 1 pharmacokinetic and drug-interaction study of dasatinib in patients with advanced solid tumors. Cancer 2010;116:1582-1591.
97. Pusztai L, Moulder SL, Litton JK et al. Gene-signature-based patient selection for dasatinib therapy in metastatic breast cancer (MBC). J Clin Oncol 2010;28(15 suppl):Abstract TPS130.
98. Tsao AS, Wistuba II, Mehran RJ. Evaluation of Src Tyr419 as a predictive biomarker in a neoadjuvant trial using dasatinib in resectable malignant pleural mesothelioma. J Clin Oncol 2010;28(15 suppl):Abstract 7042.
99. Schuetze S, Wathen K, Choy E et al. Results of a Sarcoma Alliance for Research through Collaboration (SARC) phase II trial of dasatinib in previously treated, high-grade, advanced sarcoma. J Clin Oncol 2010;28(15 suppl):Abstract 10009.
100. +) metastatic breast cancer (MBC). J Clin Oncol 2010;28(suppl):Abstract e13074.