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Molecular targeted therapy in epithelial ovarian cancer

Year 2013, Volume: 18 Issue: 3, 101 - 107, 21.02.2013

Şenol Şentürk İşık Üstüner E. Seda Güven

Abstract

Ovarian cancer is the most common cause of mortality of tumors from gynecologic origin and is often diagnosed after patients have already progressed to advanced disease stage. The current standard of care for treatment of epithelial ovarian cancer includes cytoreductive surgery followed by adjuvant chemotherapy. However, the development of resistance, disease recurrence and poor prognosis is still the most important problems. Despite enhancements in tumor debulking surgery and combination regimens, the majority of ovarian cancer patients not only experience adverse effects, but also eventually relapses. Therefore, additional therapeutic possibilities need to be explored to minimize adverse events and prolong progression-free survival and overall response rates in ovarian cancer patients. Recent advances in the understanding of molecular mechanisms and genetics of epithelial ovarian cancer have led to the identification of new targets.

In this review we focus on the molecular mechanisms and the clinical efficacy of molecular targeted therapy on epithelial ovarian cancer.

Keywords

Angiogenesis apoptosis epithelial ovarian cancer molecular targeted therapy receptors

References

  • Demirkan HM, Güler N. Targeted Therapies in Female Genital System Cancers (Vulvar, Vaginal, Cervical, Endometrial, Ovarian, and Fallopian Tube Cancers, Gestational Trophoblastic Tumors). Turkiye Klinikleri J Med Oncol-Special Topics 2011; 4: 1351
  • Güngör M, Kahraman K. Targeted therapy for epithelial ovarian cancer. Turkiye Klinikleri J Surg Med Sci 2007; 3: 63-69.
  • Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001 CA Cancer J Clin 2001; 51: 15Bookman MA. Standart treatment in advanced ovarian cancer in 2005: the state of the art. Int J Gynecol Cancer 2005; 15: 212-220.
  • Jacobs IJ, Kohler MF, Wiseman R, et al. Clonal origin of epithelial ovarian cancer: Analysis by loss of heterozygosity, p53 mutation and X chromosome inactivation. J Natl Cancer Ins 1992; 84: 1793-1798.
  • See HT, Kavanagh JJ, Hu W, Bast RC. Targeted therapy for epithelial ovarian cancer. Int J Gynecol Cancer 2003; 13: 701-734.
  • Darcy KM, Schilder RJ. Relevant molecular markers and targets. Gynecol Oncol 2006; 103: 6-13.
  • Willmott LJ, Fruehauf JP. Targeted therapy in ovarian cancer. J Oncol 2010; 2010: 740472.
  • Dean E, El-Helw L, Hasan J. Targeted Therapies in Epithelial Ovarian Cancer. Cancers 2010; 2: 88-113.
  • Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005; 438: 967-974.
  • Itamochi H, Kigawa J. Clinical trials and future potential of targeted therapy for ovarian cancer. Int J Clin Oncol 2012; 17: 430-440.
  • Brown MR, Blanchette JO, Kohn EC. Angiogenesis in ovarian cancer. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 901-918.
  • Siddiqui GK, Maclean AB, Elmasry K et al. Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer. Angiogenesis 2011; 14: 155-1
  • Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342.
  • Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666-2676.
  • Sandler A, Gray R, Perry MC, et al. Paclitaxelcarboplatin alone or with bevacizumab for non-smallcell lung cancer. N Engl J Med 2006; 355: 2542-2550.
  • Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8: 579-591.
  • Monk BJ, Choi DC, Pugmire G, Burger RA. Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer. Gynecol Oncol 2005; 96: 902-905.
  • Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II Trial of Bevacizumab in Persistant or Recurrent Epithelial Ovarian Cancer or Primary Peritoneal Cancer. A Gynecologic Oncology Group Study. J Clin Oncol 2007; 25: 5165-5171.
  • Garcia AA, Hirte H, Fleming G, et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: A trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia. J Clin Oncol 2008; 26: 76Cohn DE, Valmadre S, Resnick KE, et al. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecol Oncol 2006; 102: 134-139.
  • Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinumresistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007; 25: 5180-5186.
  • Micha JP, Goldstein BH, Rettenmaier MA, et al. A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer. Int J Gynecol Cancer 2007; 17: 771-776.
  • Penson RT, Dizon DS, Cannistra SA, et al. Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol 2010; 28: 154-1
  • Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365: 2484-2496.
  • Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-2483.
  • Stark D, Nankivell M, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol 2013; 14: 236-243.
  • Gotlieb WH, Amant F, Advani S, et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind,placebocontrolled study. Lancet Oncol 2012; 13: 154-162.
  • Ramasubbaiah R, Perkins SM, Schilder J, et al. Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group. Gynecol Oncol 2011; 123: 499-50
  • Annunziata CM, Walker AJ, Minasian L, et al. Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Clin Cancer Res 2010; 16: 664-672.
  • Matulonis UA, Berlin S, Ivy P, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 2009; 27: 5601-5606.
  • Zweifel M, Jayson G, Reed N, et al. Combretastatin A-4 phosphate (Ca4p) carboplatin and paclitaxel in patients with platinum-resistant ovarian cancer: Final phase II trial results. J Clin Oncol 2009; 27: Abstract 550
  • Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med 2008; 358: 1160-1174.
  • Berchuck A, Rodriguez GC, Kamel A, et al. Epidermal Growth Factor expression in normal ovarian epithelium and ovarian cancer. Correlation of recetor expression with prognostic factors in patients with ovarian cancer. Am J Obstet Gynecol 1991; 164: 669-6
  • Niikura H, Sasano H, Sato S, Yajima A. Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors. Int J Gynecol Pathol 1997; 16: 60-68.
  • Tanaka Y, Miyamoto S, Suzuki SO, et al. Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res 2005; 11: 4783-4792.
  • D'Antonio A, Losito S, Pignata S, et al. Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas. Int J Oncol 2002; 21: 941-948.
  • Dorigo O, Martinez-Maza O, Berek JS. Biologic, Targeted, and Immune Therapies. In: Berek JS, Hacker NF, eds. Practical Gynecologic Oncology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010: p.41-56.
  • Ledermann J, Raja FA. Targeted trials in ovarian cancer. Gynecol Oncol 2010; 119: 151-156.
  • Makhija S, Amler LC, Glenn D, et al. Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J Clin Oncol 2010; 28: 1215-1223.
  • Sourbier C. Ovarian cancer: emerging moleculartargeted therapies. Biologics 2012; 6: 147-154.
  • Gordon AN, Finkler N, Edwards RP et al. Efficacy and 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: 785-792.
  • Vergote IB, Joly F, Katsaros D, et al. Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a GCIG and EORTC-GCG study. J Clin Oncol 2012; 30: LBA5000.
  • Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2012; 12: 68-78.
  • Cass I, Baldwin RL, Varkey T, et al. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 2003; 97: 2187-2195.
  • Tan DS, Rothermundt C, Thomas K, et al. “BRCAness” syndrome in ovarian cancer: a casecontrol study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J Clin Oncol 2008; 26: 5530–5536.
  • Audeh MW, Carmichael J, Penson RT, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 2010; 376: 245-251.
  • Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiatedovarian carcinoma or triplenegative breast cancer: a phase 2, multicentre, openlabel, non-randomised study. Lancet Oncol 2011; 12: 852-8
  • Kaye SB, Lubinski J, Matulonis U, et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADPribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol 2012; 30: 372-379.
  • Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366: 1382-1392.
  • Behbakht K, Sill MW, Darcy KM, et al. Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol Oncol 2011; 123: 19-26.

Year 2013, Volume: 18 Issue: 3, 101 - 107, 21.02.2013

Şenol Şentürk İşık Üstüner E. Seda Güven

Abstract

References

  • Demirkan HM, Güler N. Targeted Therapies in Female Genital System Cancers (Vulvar, Vaginal, Cervical, Endometrial, Ovarian, and Fallopian Tube Cancers, Gestational Trophoblastic Tumors). Turkiye Klinikleri J Med Oncol-Special Topics 2011; 4: 1351
  • Güngör M, Kahraman K. Targeted therapy for epithelial ovarian cancer. Turkiye Klinikleri J Surg Med Sci 2007; 3: 63-69.
  • Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001 CA Cancer J Clin 2001; 51: 15Bookman MA. Standart treatment in advanced ovarian cancer in 2005: the state of the art. Int J Gynecol Cancer 2005; 15: 212-220.
  • Jacobs IJ, Kohler MF, Wiseman R, et al. Clonal origin of epithelial ovarian cancer: Analysis by loss of heterozygosity, p53 mutation and X chromosome inactivation. J Natl Cancer Ins 1992; 84: 1793-1798.
  • See HT, Kavanagh JJ, Hu W, Bast RC. Targeted therapy for epithelial ovarian cancer. Int J Gynecol Cancer 2003; 13: 701-734.
  • Darcy KM, Schilder RJ. Relevant molecular markers and targets. Gynecol Oncol 2006; 103: 6-13.
  • Willmott LJ, Fruehauf JP. Targeted therapy in ovarian cancer. J Oncol 2010; 2010: 740472.
  • Dean E, El-Helw L, Hasan J. Targeted Therapies in Epithelial Ovarian Cancer. Cancers 2010; 2: 88-113.
  • Ferrara N, Kerbel RS. Angiogenesis as a therapeutic target. Nature. 2005; 438: 967-974.
  • Itamochi H, Kigawa J. Clinical trials and future potential of targeted therapy for ovarian cancer. Int J Clin Oncol 2012; 17: 430-440.
  • Brown MR, Blanchette JO, Kohn EC. Angiogenesis in ovarian cancer. Baillieres Best Pract Res Clin Obstet Gynaecol 2000; 14: 901-918.
  • Siddiqui GK, Maclean AB, Elmasry K et al. Immunohistochemical expression of VEGF predicts response to platinum based chemotherapy in patients with epithelial ovarian cancer. Angiogenesis 2011; 14: 155-1
  • Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342.
  • Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007; 357: 2666-2676.
  • Sandler A, Gray R, Perry MC, et al. Paclitaxelcarboplatin alone or with bevacizumab for non-smallcell lung cancer. N Engl J Med 2006; 355: 2542-2550.
  • Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 2008; 8: 579-591.
  • Monk BJ, Choi DC, Pugmire G, Burger RA. Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer. Gynecol Oncol 2005; 96: 902-905.
  • Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II Trial of Bevacizumab in Persistant or Recurrent Epithelial Ovarian Cancer or Primary Peritoneal Cancer. A Gynecologic Oncology Group Study. J Clin Oncol 2007; 25: 5165-5171.
  • Garcia AA, Hirte H, Fleming G, et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: A trial of the California, Chicago, and Princess Margaret Hospital Phase II Consortia. J Clin Oncol 2008; 26: 76Cohn DE, Valmadre S, Resnick KE, et al. Bevacizumab and weekly taxane chemotherapy demonstrates activity in refractory ovarian cancer. Gynecol Oncol 2006; 102: 134-139.
  • Cannistra SA, Matulonis UA, Penson RT, et al. Phase II study of bevacizumab in patients with platinumresistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007; 25: 5180-5186.
  • Micha JP, Goldstein BH, Rettenmaier MA, et al. A phase II study of outpatient first-line paclitaxel, carboplatin, and bevacizumab for advanced-stage epithelial ovarian, peritoneal, and fallopian tube cancer. Int J Gynecol Cancer 2007; 17: 771-776.
  • Penson RT, Dizon DS, Cannistra SA, et al. Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. J Clin Oncol 2010; 28: 154-1
  • Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365: 2484-2496.
  • Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-2483.
  • Stark D, Nankivell M, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol 2013; 14: 236-243.
  • Gotlieb WH, Amant F, Advani S, et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind,placebocontrolled study. Lancet Oncol 2012; 13: 154-162.
  • Ramasubbaiah R, Perkins SM, Schilder J, et al. Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group. Gynecol Oncol 2011; 123: 499-50
  • Annunziata CM, Walker AJ, Minasian L, et al. Vandetanib, designed to inhibit VEGFR2 and EGFR signaling, had no clinical activity as monotherapy for recurrent ovarian cancer and no detectable modulation of VEGFR2. Clin Cancer Res 2010; 16: 664-672.
  • Matulonis UA, Berlin S, Ivy P, et al. Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer. J Clin Oncol 2009; 27: 5601-5606.
  • Zweifel M, Jayson G, Reed N, et al. Combretastatin A-4 phosphate (Ca4p) carboplatin and paclitaxel in patients with platinum-resistant ovarian cancer: Final phase II trial results. J Clin Oncol 2009; 27: Abstract 550
  • Ciardiello F, Tortora G. EGFR antagonists in cancer treatment. N Engl J Med 2008; 358: 1160-1174.
  • Berchuck A, Rodriguez GC, Kamel A, et al. Epidermal Growth Factor expression in normal ovarian epithelium and ovarian cancer. Correlation of recetor expression with prognostic factors in patients with ovarian cancer. Am J Obstet Gynecol 1991; 164: 669-6
  • Niikura H, Sasano H, Sato S, Yajima A. Expression of epidermal growth factor-related proteins and epidermal growth factor receptor in common epithelial ovarian tumors. Int J Gynecol Pathol 1997; 16: 60-68.
  • Tanaka Y, Miyamoto S, Suzuki SO, et al. Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer. Clin Cancer Res 2005; 11: 4783-4792.
  • D'Antonio A, Losito S, Pignata S, et al. Transforming growth factor alpha, amphiregulin and cripto-1 are frequently expressed in advanced human ovarian carcinomas. Int J Oncol 2002; 21: 941-948.
  • Dorigo O, Martinez-Maza O, Berek JS. Biologic, Targeted, and Immune Therapies. In: Berek JS, Hacker NF, eds. Practical Gynecologic Oncology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010: p.41-56.
  • Ledermann J, Raja FA. Targeted trials in ovarian cancer. Gynecol Oncol 2010; 119: 151-156.
  • Makhija S, Amler LC, Glenn D, et al. Clinical activity of gemcitabine plus pertuzumab in platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. J Clin Oncol 2010; 28: 1215-1223.
  • Sourbier C. Ovarian cancer: emerging moleculartargeted therapies. Biologics 2012; 6: 147-154.
  • Gordon AN, Finkler N, Edwards RP et al. Efficacy and 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: 785-792.
  • Vergote IB, Joly F, Katsaros D, et al. Randomized phase III study of erlotinib versus observation in patients with no evidence of disease progression after first-line platin-based chemotherapy for ovarian carcinoma: a GCIG and EORTC-GCG study. J Clin Oncol 2012; 30: LBA5000.
  • Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2012; 12: 68-78.
  • Cass I, Baldwin RL, Varkey T, et al. Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 2003; 97: 2187-2195.
  • Tan DS, Rothermundt C, Thomas K, et al. “BRCAness” syndrome in ovarian cancer: a casecontrol study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations. J Clin Oncol 2008; 26: 5530–5536.
  • Audeh MW, Carmichael J, Penson RT, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 2010; 376: 245-251.
  • Gelmon KA, Tischkowitz M, Mackay H, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiatedovarian carcinoma or triplenegative breast cancer: a phase 2, multicentre, openlabel, non-randomised study. Lancet Oncol 2011; 12: 852-8
  • Kaye SB, Lubinski J, Matulonis U, et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADPribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol 2012; 30: 372-379.
  • Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366: 1382-1392.
  • Behbakht K, Sill MW, Darcy KM, et al. Phase II trial of the mTOR inhibitor, temsirolimus and evaluation of circulating tumor cells and tumor biomarkers in persistent and recurrent epithelial ovarian and primary peritoneal malignancies: a Gynecologic Oncology Group study. Gynecol Oncol 2011; 123: 19-26.
There are 49 citations in total.

Details

Primary Language English
Journal Section Articles
Authors

Şenol Şentürk

İşık Üstüner

E. Seda Güven This is me

Publication Date February 21, 2013
Published in Issue Year 2013 Volume: 18 Issue: 3

Cite

APA Şentürk, Ş., Üstüner, İ., & Güven, E. S. (2013). Molecular targeted therapy in epithelial ovarian cancer. EASTERN JOURNAL OF MEDICINE, 18(3), 101-107.
AMA Şentürk Ş, Üstüner İ, Güven ES. Molecular targeted therapy in epithelial ovarian cancer. EASTERN JOURNAL OF MEDICINE. October 2013;18(3):101-107.
Chicago Şentürk, Şenol, İşık Üstüner, and E. Seda Güven. “Molecular Targeted Therapy in Epithelial Ovarian Cancer”. EASTERN JOURNAL OF MEDICINE 18, no. 3 (October 2013): 101-7.
EndNote Şentürk Ş, Üstüner İ, Güven ES (October 1, 2013) Molecular targeted therapy in epithelial ovarian cancer. EASTERN JOURNAL OF MEDICINE 18 3 101–107.
IEEE Ş. Şentürk, İ. Üstüner, and E. S. Güven, “Molecular targeted therapy in epithelial ovarian cancer”, EASTERN JOURNAL OF MEDICINE, vol. 18, no. 3, pp. 101–107, 2013.
ISNAD Şentürk, Şenol et al. “Molecular Targeted Therapy in Epithelial Ovarian Cancer”. EASTERN JOURNAL OF MEDICINE 18/3 (October 2013), 101-107.
JAMA Şentürk Ş, Üstüner İ, Güven ES. Molecular targeted therapy in epithelial ovarian cancer. EASTERN JOURNAL OF MEDICINE. 2013;18:101–107.
MLA Şentürk, Şenol et al. “Molecular Targeted Therapy in Epithelial Ovarian Cancer”. EASTERN JOURNAL OF MEDICINE, vol. 18, no. 3, 2013, pp. 101-7.
Vancouver Şentürk Ş, Üstüner İ, Güven ES. Molecular targeted therapy in epithelial ovarian cancer. EASTERN JOURNAL OF MEDICINE. 2013;18(3):101-7.