ABL1, SRC and Other Non‑ Receptor Protein Tyrosine Kinases as New Targets for Specific Anticancer Therapy
Authors:
P. Klener 1,2; Klener P. Jr 1,3
Authors‘ workplace:
I. interní klinika – klinika hematologie VFN a 1. LF UK v Praze
1; Ústav hematologie a krevní transfuze, Praha
2; Ústav patologické fyziologie 1. LF UK v Praze
3
Published in:
Klin Onkol 2010; 23(4): 203-209
Category:
Reviews
Overview
Non‑ receptor protein tyrosine kinases are responsible for signal transduction during many physiologic cellular processes, including cell growth and proliferation, apoptosis, differentiation, regulation of actin cytoskeleton, cell shape, adhesion, motility and migration. Aberrant activity of protein tyrosine kinases (acquired as a result of chromosomal translocation or point mutation) has been implicated in the stimulation of cancer growth and progression, the induction of drug‑resistance, tumour neovascularization, tissue invasion, extravasation and the formation of metastases. Small molecule tyrosine kinase inhibitors interfere with these pathophysiological circuits by blocking the signalling cascades triggered by the aberrantly activated protein tyrosine kinases (e. g. BCR‑ ABL1, FIP1L1- PDGFRA or ETV6- PDGFRB). Tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib) now belong to established anti‑cancer agents with clinical activity in patients with CML, Ph+ ALL, and myeloid neoplasms with overexpression of PDGFRA, PDGFRB and wild‑type KIT. New generation tyrosine kinase inhibitors (e. g. dasatinib) with extended activity against SRC and EPH kinases belong to promising anti‑cancer agents with documented preclinical activity in several solid tumours (e. g. prostate cancer).
Key words:
non‑receptor tyrosine kinases – SRC – BCR‑ ABL1 – TKI – imatinib – nilotinib – dasatinib – CML – solid tumours – prostate cancer – bone metastases
Sources
1. Pierotti MA, Negri T, Tamborini E et al. Targeted therapies: The rare cancer paradigm. Molecular Oncology 2010; 4(1): 19– 37.
2. Klener P, Klener P Jr. Nová protinádorová léčiva a léčebné strategie v onkologii. Praha: Grada Publishing; , 2010.
3. Rous P. A sarcoma of the fowl transmissible by an agent separable from tumor cells. J Exp Med 1911; 13(4): 397– 411.
4. Guarino M. Src signaling in cancer invasion. J Cell Physiol 2010; 223(1): 14– 26.
5. Tsygankov AY, Shore SK. Src: regulation, role in human carcinogenesis and pharmacological inhibitors. Curr Pharm Des 2004; 10(15): 1745– 1756.
6. Eliceiri BP, Paul R, Schwartzberg PL et al. Selective requirement for src kinase during VEGF‑induced angiogenesis and vascular permeability. Mol Cell 1999; 4(6): 915– 924.
7. Summy JM, Gallick GE. Src family kinase in tumor progression and metastasis. Cancer Metastasis Rev 2003; 22(4): 337– 358.
8. Roodman GD. Mechanisms of bone metastasis. New Engl J Med 2004; 350(16): 353– 259.
9. Aligayer H, Boyd DD, Heiss MM et al. Activation of src in primary colorectal carcinoma: an indicator of poor prognosis. Cancer 2002; 94(2): 344– 351.
10. Kopetz S, Shah AN, Gallick GE. Src continues aging: Current and future clinical directions. Clin Cancer Res 2007; 13(24): 7232– 7236.
11. Kim LC, Song L, Haura EB. Src kinases as therapeutic targets for cancer. Nat Rev Clin Oncol 2009; 6(10): 587– 595.
12. Zhao J, Guan JL. Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev 2009; 28(1– 2): 35– 49.
13. Provenzano PP, Keely PJ. The role of focal adhesion kinase in tumor initiation and progression. Cell Adh Mgr 2009; 3(4): 347– 350.
14. Bruton VG, Frame MC. Src and focal adhesion kinase as therapeutic targets in cancer. Curr Opin Pharmacol 2008; 8(4): 1– 6.
15. Naomomto HH, Watanabe BX, Sakurama K et al. Focal ahesion kinase as potential target for cancer therapy (Review). Oncol Rep 2009; 22(5): 973– 979.
16. Klener P, Klamová H. Imatinib – nová perspektiva v léčbě nádorových onemocnění. Čas Lék čes 2004; 143: 577– 581.
17. Deremer DL, Ustun C, Natarajan K. Nilotinib: a second‑ generation tyrosin kinase inhibitor of chronic myelogenous leukemia. Clin Ther 2008; 30(11): 1956– 1975.
18. Kim LC, Haura EB. Dasatinib in solid tumors. Expert Opin Investig Drugs 2010; 19(3): 415– 425.
19. Hu Y, Swerdlow S, Duffy TM et al. Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. PNAS 2006: 103(45): 16870– 16875.
20. Araujo J, Logothetis C. Dasatinib: A potent SRC inhibitor in clinical development for treatment of solid tumors. Cancer Treat Rew 2010; Epub ehaed of print.
21. Fizazi K. The role of src in prostate cancer. Ann Oncol 2007; 18(11): 1765– 1773.
22. 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(20): 9185– 9189.
23. Araujo 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 (Suppl): 15.
24. Park SI, Zhang J, Phillips KA et al. Targeting Src family kinases inhibits growth and lymph nodes metastases of prostate cancer in an orthotopic nude mouse model. Cancer Res 2008; 68: 3323– 3333.
25. Koreckij T, Nguyen H, Brown LG et al. Dasatinib inhibits the growth of prostate cancer in bone and provides additional protection from osteolysis. Brit J Cancer 2009; 101(2): 263– 268.
26. Finn RS. Targeting src in breast cancer. Ann Oncol 2008; 19(8): 1379– 1386.
27. Dizdar O, Dede DS, Bulut N et al. Dasatinib may inhibit c‑ kit in triple negative breast cancer cell lines. Breast Cancer Res Treat 2009; 107(2): 303– 305.
28. Du J, Bernasconi P, Clauser KR et al. Bead‑based profiling of tyrosine kinase phosphorylation identifies src as a potential target for glioblastoma therapy. Nat Biotechnol 2009; 27(1): 77– 83.
29. GIG Media Group. Selected clinical trials in colorectal cancer. Clin Colorectal Cancer 2008; 7: 69.
30. Ito H, Gardber‑ Thorpe J, Zinner MJ et al. Inhibition of tyrosinkinase src suppress pancreatic cancer invasiveness. Surgery 2003; 134(2): 221– 226.
31. Shor AC, Keschman EA, Lee FY et al. Dasatinib inhibits migration and invasion in divers human sarcoma cell lines and induces apoptosis in bone sarcoma cells dependent on Src kinase for survival. Cancer Res 2007; 67(6): 2800– 2808.
32. Saad F. Src as therapeutic target in men with prostate cancer and bone metastases BJU Int. 2009; 103(4): 434– 440.
33. Keller G, Schafhausen P, Brummendorf TH. Bosutinib. Recent Results Cancer Rev 2010; 184: 119– 127.
34. Dulsat C, Mealy N, Castaner R. Saracatinib. Drugs Fut 2009; 34(2): 106.
35. Tabernero J, Cervantes A, Hoekman K et al. Phase I study of AZD0530, an oral potent inhibitor of src kinase: First demonstration of inhibition of Src activity in human cancers. J Clin Oncol 2007; ASCO Ann Meeting Proc; 23: 3520.
36. Green TP, Fennell M, Whittaker R. Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol 2009; 3: 248– 261.
37. 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 Endokrin Metab 2009, 94(6): 2199– 2203.
38. Kantarjian H, Coutre PL, Cortes J et al. Phase 1 study of INNO‑ 406, a dual Abl/ Lyn kinase inhibitor, in Philadelphia chromosome‑ positive leukemias after imatinib resistance or intolerance. Cancer 2010 (epub ahead of print).
39. Cohen RB, Jones SF, Aggarwal C et al. A phase I dose‑escalation study of danusertib (PHA‑ 739358) administered as a 24- hour infusion with and without granulocyte colony‑ stimulating factor in a 14- day cycle in patients with advanced solid tumors. Clin Cancer Res 2009; 15: 6694– 6701.
40. Roberts WG, Ung E, Ehalen P et al. Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF‑ 562, 271. Cancer Res 2008; 68(6): 1935– 1944.
41. Wheeler DL, Lida M, Kruser TJ et al. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab. Cancer Biol Ther 2209; 8(8): 696– 703.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2010 Issue 4
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