|
|
Molecular targeted therapy of gynecological malignant
tumors: the development and challenge, from laboratory to clinic |
Pengming SUN PhD, MD 1, Jalid SEHOULI PhD, MD 2, Lihui WEI BM 3, |
1.Institute of Gynecologic
Oncology, Fujian Provincial Women and Children''s Hospital, Fujian
Medical University, Fuzhou 350001, China;Department of Gynecology,
Campus Virchow Klinikum, Berlin 13353, Germany; 2.Department of Gynecology,
Campus Virchow Klinikum, Berlin 13353, Germany; 3.Department of Gynecology,
Peking University People’s Hospital, Beijing 100044, China; |
|
|
Abstract More and more molecular drugs based on targeted therapy have been utilized in the treatment of gynecologic cancer, especially in ovarian cancer. In this article, we systematically review the current targeted therapeutic trials running in clinic. Large, randomized trials have been conducted in the treatment of ovarian cancer, endometrial cancer and cervical cancer by using small molecule, antisense, mutational gene as well as antibodies. Other planned or ongoing trials currentlytargeted at molecular markers which may play important roles in gynecological carcinogenesis andprogression suggest that combination chemotherapy with molecular targeted therapy will ultimately be an importantoption.
|
Keywords
target therapy
gynecologic malignant tumors
clinical trail
molecular medicine
|
Issue Date: 05 September 2009
|
|
|
Rosner B A, Colditz G A, Webb P M, Hankinson S E. Mathematical models of ovarian cancer incidence. Epidemiology, 2005, 16(4): 508―515
doi: 10.1097/01.ede.0000164557.81694.63
|
|
Novac L,Grigore T , Cernea N, Niculescu M, Cotarcea S. Incidence of endometrialcarcinoma in patients with endometrial hyperplasia. Eur J Gynaecol Oncol, 2005, 26(5): 561―563
|
|
Katz I T, Wright A A. Preventing cervical cancerin the developing world. N Engl J Med, 2006, 354(11): 1110
doi: 10.1056/NEJMp068031
|
|
Farley J H, Birrer M J. Biologic directed therapiesin gynecologic oncology. Curr Oncol Rep, 2003, 5(6): 459―467
doi: 10.1007/s11912-003-0006-x
|
|
Qian C, Prieto J. Gene therapy of cancer: inductionof anti-tumor immunity. Cell Mol Immunol, 2004, 1(2): 105―111
|
|
Copland M, Jorgensen H G, Holyoake T L. Evolving molecular therapy for chronic myeloid leukaemia--arewe on target? Hematology, 2005, 10(5): 349―359
doi: 10.1080/10245330500234195
|
|
Stipsanelli E, Valsamaki P. Monoclonal antibodies: oldand new trends in breast cancer imaging and therapeutic approach. Hell J Nucl Med, 2005, 8(2): 103―108
|
|
Zhang Z, Li M, Rayburn E R, Hill D L, Zhang R, Wang H. Oncogenesas novel targets for cancer therapy (part II): Intermediate signalingmolecules. Am J Pharmacogenomics, 2005, 5(6): 247―257
doi: 10.2165/00129785-200505040-00005
|
|
Sharma S, Odunsi K. Targeted therapy for epithelialovarian cancer. Expert Opin Ther Targets, 2005, 9(3): 501―513
doi: 10.1517/14728222.9.3.501
|
|
Hyde J, McMeekin D S. Targeted therapies for gynecologicmalignancies. Curr Treat Options Oncol, 2005, 6(2): 121―132
doi: 10.1007/s11864-005-0020-3
|
|
Kumar R, Hung M C. Signaling intricacies takecenter stage in cancer cells. Cancer Res, 2005, 65(7): 2511―2515
doi: 10.1158/0008-5472.CAN-05-0189
|
|
Haupt S, Berger M, Goldberg Z, Haupt Y. Apoptosis-thep53 network. J Cell Sci, 2003, 116(20): 4077―4085
doi: 10.1242/jcs.00739
|
|
Hanahan D, Weinberg R A. The hallmarks of cancer. Cell, 2000, 100(1): 57―70
doi: 10.1016/S0092-8674(00)81683-9
|
|
Sanseverino F, Torricelli M, Petraglia F, Giordano A. Roleof the retinoblastoma family in gynecological cancer. Cancer Biol Ther, 2003, 2(6): 636―641
|
|
Crowe D L, Kim R, Chandraratna R A. Retinoic acid differentially regulatescancer cell proliferation via dose-dependent modulation of the mitogen-activatedprotein kinase pathway. Mol Cancer Res, 2003, 1(7): 532―540
|
|
Katayama K, Dobashi Y, Kitagawa M, Kawai M, Kadoya Y, Kameya T. Cdk4/cyclinD1 kinase, a universal and critical regulator of apoptosis. Anticancer Res, 2003, 23(1A): 235―243
|
|
Mammas I N, Zafiropoulos A, Spandidos D A. Involvement of the ras genes in female genital tractcancer. Int J Oncol, 2005, 26(5): 1241―1255
|
|
Wang Y, Kristensen G B, Helland A, Nesland J M, Borresen-Dale A L, Holm R. Protein expression and prognostic value of genes in theerb-b signaling pathway in advanced ovarian carcinomas. Am J Clin Pathol, 2005, 124(3): 392―401
doi: 10.1309/BL7EMW66LQX6GFRP
|
|
Hennessy B T, Smith D L, Ram P T, Lu Y, Mills G B. Exploiting the PI3K/AKT pathway for cancerdrug discovery. Nat Rev Drug Discov, 2005, 4(12): 988―1004
doi: 10.1038/nrd1902
|
|
Thomas G V. mTOR and cancer: reason for dancing at the crossroads? Curr Opin Genet Dev, 2006, 16(1): 78―84
doi: 10.1016/j.gde.2005.12.003
|
|
Choo A Y, Blenis J. TORgeting oncogene addictionfor cancer therapy. Cancer Cell, 2006, 9(2): 77―79
doi: 10.1016/j.ccr.2006.01.021
|
|
Chen H, Ye D, Xie X, Chen B, Lu W. VEGF, VEGFRs expressions and activated STATs in ovarianepithelial carcinoma. Gynecol Oncol, 2004, 94(3): 630―635
doi: 10.1016/j.ygyno.2004.05.056
|
|
Hirano T, Shino Y, Saito T, Komoda F, Okutomi Y, Takeda A, Ishihara T, Yamaguchi T, Saisho H, Shirasawa H. Dominantnegative MEKK1 inhibits survival of pancreatic cancer cells. Oncogene, 2002, 21(38): 5923―5928
doi: 10.1038/sj.onc.1205643
|
|
Silver D L, Naora H, Liu J, Cheng W, Montell D J. Activated signal transducer and activatorof transcription (STAT) 3: localization in focal adhesions and functionin ovarian cancer cell motility. CancerRes, 2004, 64(10): 3550―3558
doi: 10.1158/0008-5472.CAN-03-3959
|
|
Wang S C, Hung M C. HER2 overexpression and cancertargeting. Semin Oncol, 2001, 28(5 Suppl 16): 115―124
doi: 10.1053/sonc.2001.28553
|
|
Mizuki M, Ueda S, Matsumura I, Ishiko J, Schwable J, Serve H, Kanakura Y. Oncogenicreceptor tyrosine kinase in leukemia. CellMol Biol (Noisy-le-grand), 2003, 49(6): 907―922
|
|
Hu W, Kavanagh J J. Anticancer therapy targetingthe apoptotic pathway. Lancet Oncol, 2003, 4(12): 721―729
doi: 10.1016/S1470-2045(03)01277-4
|
|
Leonard J V, Schapira A H. Mitochondrial respiratorychain disorders I: mitochondrial DNA defects. Lancet, 2000, 355(9200): 299―304
doi: 10.1016/S0140-6736(99)05225-3
|
|
Sherbet G V, Patil D. Genetic abnormalities ofcell proliferation, invasion and metastasis, with special referenceto gynaecological cancers. Anticancer Res, 2003, 23(2B): 1357―1371
|
|
Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer, 2005, 5(4): 275―284
doi: 10.1038/nrc1590
|
|
Sirotnak F M, Zakowski M F, Miller V A, Scher H I, Kris M G. Efficacy of cytotoxic agents againsthuman tumor xenografts is markedly enhanced by coadministration ofZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Clin Cancer Res, 2000, 6(12): 4885―4892
|
|
Gadducci A, Cosio S, Genazzani A R. Old and new perspectives in the pharmacological treatmentof advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapyand molecularly targeted therapies. CritRev Oncol Hematol, 2006, 58(3): 242―256
doi: 10.1016/j.critrevonc.2005.11.002
|
|
Sewell J M, Macleod K G, Ritchie A, Smyth J F, Langdon S P. Targeting the EGF receptor in ovariancancer with the tyrosine kinase inhibitor ZD 1839 ("Iressa"). British J Cancer, 2002, 86(3): 456―462
doi: 10.1038/sj.bjc.6600058
|
|
Schilder R J, Sill M W, Chen X, Darcy K M, Decesare S L, Lewandowski G, Lee R B, Arciero C A, Wu H, Godwin A K. Phase II study of gefitinibin patients with relapsed or persistent ovarian or primary peritonealcarcinoma and evaluation of epidermal growth factor receptor mutationsand immunohistochemical expression: a Gynecologic Oncology Group Study. Clin Cancer Res, 2005, 11(15): 5539―5548
doi: 10.1158/1078-0432.CCR-05-0462
|
|
Gordon A N, Finkler N, Edwards R P, Garcia A A, Crozier M, Irwin D H, Barrett E. Efficacyand safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR)tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma:results from a phase II multicenter study. Int J Gynecol Cancer, 2005, 15(5): 785―792
doi: 10.1111/j.1525-1438.2005.00137.x
|
|
Xiong H Q, Herbst R, Faria S C, Scholz C, Davis D, Jackson E F, Madden T, McConkey D, Hicks M, Hess K, Charnsangavej C A, Abbruzzese J L. A phase I surrogate endpoint study of SU6668 in patientswith solid tumors. Invest New Drugs, 2004, 22(4): 459―466
doi: 10.1023/B:DRUG.0000036688.96453.8d
|
|
Del Carmen M G, Rizvi I, Chang Y, Moor A C, Oliva E, Sherwood M, Pogue B, Hasan T. Synergism of epidermal growth factor receptor-targetedimmunotherapy with photodynamic treatment of ovarian cancer in vivo. J Natl Cancer Inst, 2005, 97(20): 1516―1524
|
|
Cohn D E, Valmadre S, Resnick K E, Eaton L A, CopelandL J, Fowler J M. Bevacizumab and weekly taxane chemotherapy demonstratesactivity in refractory ovarian cancer. Gynecol Oncol, 2006, 102(2): 131―133
doi: 10.1016/j.ygyno.2006.01.030
|
|
Bookman M A, Darcy K M, Clarke-Pearson D, Boothby R A, Horowitz I R. Evaluation of monoclonalhumanized anti-HER2 antibody, trastuzumab, in patients with recurrentor refractory ovarian or primary peritoneal carcinoma with overexpressionof HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol, 2003, 21(2): 283―290
doi: 10.1200/JCO.2003.10.104
|
|
Santin A D, Bellone S, Gokden M, Palmieri M, Dunn D, Agha J, Roman J J, Hutchins L, Pecorelli S, O'Brien T, Cannon M J, Parham G P. Overexpression of HER-2/neu in uterine serous papillary cancer. Clin Cancer Res, 2002, 8(5): 1271―1279
|
|
Oza A M, Elit L, Swenerton K, Faught W, Ghatage P, Carey M, McIntosh L, Dorr A, Holmlund J T, Eisenhauer E. PhaseII study of CGP 69846A (ISIS 5132) in recurrent epithelial ovariancancer: an NCIC clinical trials group study (NCIC IND.116). Gynecol Oncol, 2003, 89(1): 129―133
doi: 10.1016/S0090-8258(02)00144-0
|
|
Advani R, Peethambaram P, Lum B L, Fisher G A, Hartmann L, Long H J, Halsey J, Holmlund J T, Dorr A, Sikic B I. A Phase IItrial of aprinocarsen, an antisense oligonucleotide inhibitor of proteinkinase C alpha, administered as a 21-day infusion to patients withadvanced ovarian carcinoma. Cancer, 2004, 100(2): 321―326
doi: 10.1002/cncr.11909
|
|
Armstrong D K, Blessing J A, Look K Y, Schilder R, Nunez E R. A randomized phase II evaluationof bryostatin-1 (NSC #339555) in recurrent or persistent platinum-sensitiveovarian cancer: a Gynecologic Oncology Group Study. Invest New Drugs, 2003, 21(3): 373―377
doi: 10.1023/A:1025490818450
|
|
Smith V, Hobbs S, Court W, Eccles S, Workman P, Kelland L R. ErbB2 overexpression in an ovarian cancer cell line conferssensitivity to the HSP90 inhibitor geldanamycin. Anticancer Res, 2002, 22(4): 1993―1999
|
|
Aghajanian C, Dizon D S, Sabbatini P, Raizer J J, Dupont J, Spriggs D R. Phase I trial of bortezomib and carboplatin in recurrentovarian or primary peritoneal cancer. JClin Oncol, 2005, 23(25): 5943―5949
doi: 10.1200/JCO.2005.16.006
|
|
Siu L L, Awada A, Takimoto C H, Piccart M, Schwartz B, Giannaris T, Lathia C, Petrenciuc O, Moore M J. Phase I trial of sorafenib and gemcitabine in advancedsolid tumors with an expanded cohort in advanced pancreatic cancer. Clin Cancer Res, 2006, 12(1): 144―151
doi: 10.1158/1078-0432.CCR-05-1571
|
|
Buller R E, Runnebaum I B, Karlan B Y, Horowitz J A, Shahin M, Buekers T, Petrauskas S, Kreienberg R, Slamon D, Pegram M. Aphase I/II trial of rAd/p53 (SCH 58500) gene replacement in recurrentovarian cancer. Cancer Gene Ther, 2002, 9(7): 553―566
doi: 10.1038/sj.cgt.7700472
|
|
Kavanagh J J, Gershenson D M, Choi H, Lewis L, Patel K, Brown G L, Garcia A, Spriggs D R. Multi-institutional phase 2 study of TLK286 (TELCYTA,a glutathione S-transferase P1-1 activated glutathione analog prodrug)in patients with platinum and paclitaxel refractory or resistant ovariancancer. Int J Gynecol Cancer, 2005, 15(4): 593―600
doi: 10.1111/j.1525-1438.2005.00114.x
|
|
Vasey P A, Shulman L N, Campos S, Davis J, Gore M, Johnston S, Kirn D H, O'Neill V, Siddiqui N, Seiden M V, Kaye S B. Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deletedadenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeksin patients with recurrent/refractory epithelial ovarian cancer. J Clin Oncol, 2002, 20(6): 1562―1569
doi: 10.1200/JCO.20.6.1562
|
|
Geffen D B, Man S. New drugs for the treatmentof cancer, 1990-2001. Isr Med Assoc J, 2002, 4(12): 1124―1131
|
|
Libermann T A, Zerbini L F. Targeting transcription factorsfor cancer gene therapy. Curr Gene Ther, 2006, 6(1): 17―33
doi: 10.2174/156652306775515501
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|