Skip to main content

Advertisement

SpringerLink
Log in

Molecular profiling of uterine cervix carcinoma: an overview with a special focus on rationally designed target-based anticancer agents

  • NON-THEMATIC REVIEW
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Although conventional multimodality approaches allowed improvement in the prognosis of patients with cervix cancer, several tumors do not respond similarly to standard approaches. Recent advances in basic research and genomics have improved our understanding of the biologic basis of the tumor development and progression. Tumor profiling allows for more selective therapeutic strategies leading to the identification of biomarkers or indicators of treatment response and to increased clinical efficacy through development of targeted therapies. Several markers have been identified, that are involved in cellular proliferation, interaction with angiogenesis, extracellular matrice adhesion/invasion, apoptosis, cell cycle pathways and DNA repair mechanisms. In this report, molecular profiling of uterine cervix carcinoma were reviewed with a special focus on rationally designed target-based anticancer agents, in order to clarify and to summary the present state of art in these particular promising area in cervix cancer management.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Eifel, P. J. (2005). Chemoradiotherapy for cervical cancer: what next? Journal of Clinical Oncology, 23, 8277–8279.

    PubMed  Google Scholar 

  2. Gray, H. J. (2008). Primary management of early stage cervical cancer (IA1-IB) and appropriate selection of adjuvant therapy. Journal of the National Comprehensive Cancer Network, 6, 47–52.

    PubMed  Google Scholar 

  3. Moore, D. H. (2008). Chemotherapy for advanced, recurrent, and metastatic cervical cancer. Journal of the National Comprehensive Cancer Network, 6, 53–57.

    PubMed  CAS  Google Scholar 

  4. Waggoner, S. E. (2003). Cervical cancer. Lancet, 361, 2217–2225.

    PubMed  Google Scholar 

  5. Pötter, R., et al. (2006). Recommendations from gynaecological (GYN) GEC ESTRO working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiotherapy Oncology, 78, 67–77.

    Google Scholar 

  6. Lindegaard, J.C., et al. (2008). MRI-Guided 3D Optimization Significantly Improves DVH Parameters of Pulsed-Dose-Rate Brachytherapy in Locally Advanced Cervical Cancer. International Journal of Radiation Oncology Biology Physics, 71, 756–764.

    Google Scholar 

  7. Schlessinger, J. (2000). Cell signaling by receptor tyrosine kinases. Cell, 103, 211–225.

    PubMed  CAS  Google Scholar 

  8. Bonner, J. A., et al. (2006). Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. New England Journal of Medicine, 354(6), 567–578.

    PubMed  CAS  Google Scholar 

  9. Cerciello, F., et al. (2007). Is EGFR a moving target during radiotherapy of carcinoma of the uterine cervix? Gynecologic Oncology, 106(2), 394–399.

    PubMed  CAS  Google Scholar 

  10. Huang, S. M., Bock, J. M., & Harari, P. M. (1999). Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Research, 59, 1935–1940.

    PubMed  CAS  Google Scholar 

  11. Kersemaekers, A. M., et al. (1999). Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis. Clinical Cancer Research, 5(3), 577–586.

    PubMed  CAS  Google Scholar 

  12. Pillai, M. R., Jayaprakash, P. G., & Nair, M. K. (1998). Tumor-proliferative fraction and growth factor expression as markers of tumour response to radiotherapy in cancer of the uterine cervix. Journal of Cancer Research and Clinical Oncology, 124, 456–461.

    PubMed  CAS  Google Scholar 

  13. Fuchs, I., et al. (2007). The prognostic significance of human epidermal growth factor receptor correlations in squamous cell cervical carcinoma. Anticancer Research, 27(2), 959–963.

    PubMed  CAS  Google Scholar 

  14. Gaffney, D. K., et al. (2003). Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) negatively affect overall survival in carcinoma of the cervix treated with radiotherapy. International Journal of Radiation Oncology Biology Physics, 56(4), 922–928.

    CAS  Google Scholar 

  15. Kedzia, W., et al. (2002). Immunohistochemical assay of p53, cyclin D1, c-erbB2, EGFr and Ki-67 proteins in HPV-positive and HPV-negative cervical cancers. Folia Histochemica Cytobiologica, 40, 37–41.

    Google Scholar 

  16. Biesterfeld, S., et al. (1999). Absence of epidermal growth factor receptor expression in squamous cell carcinoma of the uterine cervix is an indicator of limited tumor disease. Oncology Reports, 6, 205–209.

    PubMed  CAS  Google Scholar 

  17. Soto-Cruz, I., et al. (2008). The tyrphostin B42 inhibits cell proliferation and HER-2 autophosphorylation in cervical carcinoma cell lines. Cancer Investigation, 26(2), 136–144.

    PubMed  CAS  Google Scholar 

  18. Vaidya, A. P., Parnes, A. D., & Seiden, M. V. (2005). Rationale and clinical experience with epidermal growth factor receptor inhibitors in gynecologic malignancies. Current Treatment Options in Oncology, 6(2), 103–114.

    PubMed  Google Scholar 

  19. Bellone, S., et al. (2007). Overexpression of epidermal growth factor type-1 receptor (EGF-R1) in cervical cancer: implications for Cetuximab-mediated therapy in recurrent/metastatic disease. Gynecologic Oncology, 106(3), 513–520.

    PubMed  CAS  Google Scholar 

  20. Goncalves, A., et al. (2008). A phase II trial to evaluate gefitinib as second- or third-line treatment in patients with recurring locoregionally advanced or metastatic cervical cancer. Gynecologic Oncology, 108(1), 42–46.

    PubMed  CAS  Google Scholar 

  21. Meric, J. B., et al. (2006). Cyclooxygenase-2 as a target for anticancer drug development. Critical Reviews in Oncology/Hematology, 59, 51–64.

    PubMed  Google Scholar 

  22. Ishikawa, H., et al. (2006). Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis. International Journal of Radiation Oncology Biology Physics, 66(5), 1347–1355.

    CAS  Google Scholar 

  23. Young, J. L., et al. (2008). Cyclooxygenase-2 in cervical neoplasia: a review. Gynecologic Oncology, 109(1), 140–145.

    PubMed  CAS  Google Scholar 

  24. Ferrandina, G., et al. (2002). Increased cyclooxygenase-2 expression is associated with chemotherapy resistance and poor survival in cervical cancer patients. Journal of Clinical Oncology, 20, 973–981.

    PubMed  CAS  Google Scholar 

  25. Ferrandina, G., et al. (2002). Expression of cyclooxygenase-2 (COX-2) in tumour and stroma compartments in cervical cancer: clinical implications. British Journal of Cancer, 87, 1145–1152.

    PubMed  CAS  Google Scholar 

  26. Ferrandina, G., et al. (2003). Cyclooxygenase-2 (COX-2) expression in locally advanced cervical cancer patients undergoing chemoradiation plus surgery. International Journal of Radiation Oncology Biology Physics, 55, 21–27.

    CAS  Google Scholar 

  27. Chen, H. H., et al. (2005). Increased expression of nitric oxide synthase and cyclooxygenase-2 is associated with poor survival in cervical cancer treated with radiotherapy. International Journal of Radiation Oncology Biology Physics, 63, 1093–1100.

    CAS  Google Scholar 

  28. Kim, H. J., et al. (2003). High cyclooxygenase-2 expression is related with distant metastasis in cervical cancer treated with radiotherapy. International Journal of Radiation Oncology Biology Physics, 55, 16–20.

    CAS  Google Scholar 

  29. Kim, J. Y., et al. (2001). Tumor apoptosis in cervical cancer: its role as a prognostic factor in 42 radiotherapy patients. International Journal of Cancer, 96, 305–312.

    CAS  Google Scholar 

  30. Kim, J. Y., et al. (2005). Cyclooxygenase-2 and c-erbB-2 expression in uterine cervical neoplasm assessed using tissue microarrays. Gynecologic Oncology, 97, 337–341.

    PubMed  CAS  Google Scholar 

  31. Distefano, M., et al. (2004). Concomitant radiochemotherapy plus surgery in locally advanced cervical cancer: update of clinical outcome and cyclooxygenase-2 as predictor of treatment susceptibility. Oncology, 67, 103–111.

    PubMed  CAS  Google Scholar 

  32. Riou, G., et al. (1987). C-myc proto-oncogene expression and prognosis in early carcinoma of the uterine cervix. Lancet, 1, 761–763.

    PubMed  CAS  Google Scholar 

  33. Riou, G. F., Bourhis, J., & Le, M. G. (1990). The c-myc proto-oncogene in invasive carcinomas of the uterine cervix: clinical relevance of overexpression in early stages of the cancer. Anticancer Research, 10, 1225–1231.

    PubMed  CAS  Google Scholar 

  34. Bourhis, J., et al. (1990). Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix. Journal of Clinical Oncology, 8, 1789–1796.

    PubMed  CAS  Google Scholar 

  35. Riou, G., et al. (1988). Somatic deletions and mutations of c-Ha-ras gene in human cervical cancers. Oncogene, 3, 329–333.

    PubMed  CAS  Google Scholar 

  36. Baykal, C., et al. (2003). Overexpression of the c-Met/HGF receptor and its prognostic significance in uterine cervix carcinomas. Gynecologic Oncology, 88, 123–129.

    PubMed  CAS  Google Scholar 

  37. Markowska, J., et al. (2007). Significance of hypoxia in uterine cervical cancer. Multicentre study. European Journal of Gynaecologic Oncology, 28(5), 386–388.

    CAS  Google Scholar 

  38. Semenza, G. L. (2003). Targeting HIF-1 for cancer therapy. Nature Review Cancer, 3, 721–732.

    CAS  Google Scholar 

  39. Bachtiary, B., et al. (2003). Overexpression of hypoxia-inducible factor 1 α indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancer. Clinical Cancer Research, 9, 2234–2240.

    PubMed  CAS  Google Scholar 

  40. Birner, P., et al. (2000). Overexpression of hypoxia-inducible factor 1 alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Research, 60, 4693–4696.

    PubMed  CAS  Google Scholar 

  41. Ishikawa, H., et al. (2004). Expression of hypoxic-inducicle factor 1alpha predicts metastasis-free survival after radiation therapy alone in stage IIIB cervical squamous cell carcinoma. International Journal of Radiation Oncology Biology Physics, 60, 513–521.

    CAS  Google Scholar 

  42. Mayer, A., et al. (2004). Lack of correlation between expression of HIF-1α protein and oxygenation status in identical tissue areas of squamous cell carcinomas of the uterine cervix. Cancer Research, 64, 5876–5881.

    PubMed  CAS  Google Scholar 

  43. Quintero, M., Mackenzie, N., & Brennan, P. A. (2004). Hypoxia-inducible factor 1 (HIF-1α) in cancer. European Journal of Surgical Oncology, 30, 465–468.

    PubMed  CAS  Google Scholar 

  44. Hutchison, G. J., et al. (2004). Hypoxia-inducible factor 1α expression as an intrinsic marker of hypoxia: correlation with tumor oxygen, pimonidazole measurements, and outcome in locally advanced carcinoma of the cervix. Clinical Cancer Research, 10, 8405–8412.

    PubMed  CAS  Google Scholar 

  45. Kawanaka, T., et al. (2008). Prognostic significance of HIF-2alpha expression on tumor infiltrating macrophages in patients with uterine cervical cancer undergoing radiotherapy. Journal of Medical Investigation, 55(1–2), 78–86.

    PubMed  Google Scholar 

  46. Santin, A. D., et al. (1999). Secretion of vascular endothelial growth factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix. Obstetrics & Gynecology, 94, 78–82.

    CAS  Google Scholar 

  47. Lee, J. S., et al. (2002). Expression of vascular endothelial growth factor in adenocarcinomas of the uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein expression. Gynecologic Oncology, 85, 469–475.

    PubMed  CAS  Google Scholar 

  48. Soufla, G., et al. (2005). VEGF, FGF2, TGFB1 and TGFBR1 mRNA expression levels correlate with the malignant transformation of the uterine cervix. Cancer Letters, 221(1), 105–118.

    PubMed  CAS  Google Scholar 

  49. Bachtiary, B., et al. (2002). Serum VEGF levels in patients undergoing primary radiotherapy for cervical cancer: impact on progression-free survival. Cancer Letters, 179, 197–03.

    PubMed  CAS  Google Scholar 

  50. Cheng, W. F., et al. (2000). Vascular endothelial growth factor and prognosis of cervical carcinoma. Obstetrics & Gynecology, 96, 721–726.

    CAS  Google Scholar 

  51. Baritaki, S., et al. (2007). Overexpression of VEGF and TGF-beta1 mRNA in Pap smears correlates with progression of cervical intraepithelial neoplasia to cancer: implication of YY1 in cervical tumorigenesis and HPV infection. International Journal of Oncology, 31(1), 69–79.

    PubMed  CAS  Google Scholar 

  52. Lee, I. J., et al. (2002). Prognostic value of vascular endothelial growth factor in stage IB carcinoma of the uterine cervix. International Journal of Radiation Oncology Biology Physics, 54, 768–779.

    CAS  Google Scholar 

  53. Loncaster, J. A., et al. (2000). Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. British Journal of Cancer, 83, 620–625.

    PubMed  CAS  Google Scholar 

  54. Kang, J. O., & Hong, S. E. (2004). The prognostic effect of VEGF expression in squamous cell carcinoma of the cervix treated with radiation therapy alone. Journal of Korean Medical Science, 19, 693–697.

    Article  PubMed  CAS  Google Scholar 

  55. Airley, R., et al. (2001). Glucose transporter glut-1 expression correlates with tumor hypoxia and predicts metastasis-free survival in advanced carcinoma of the cervix. Clinical Cancer Research, 7(4), 928–934.

    PubMed  CAS  Google Scholar 

  56. Lee, W. Y., et al. (2008). Roles for hypoxia-regulated genes during cervical carcinogenesis: somatic evolution during the hypoxia-glycolysis-acidosis sequence. Gynecologic Oncology, 108(2), 377–384.

    PubMed  CAS  Google Scholar 

  57. Goh, P. P., Sze, D. M., & Roufogalis, B. D. (2007). Molecular and cellular regulators of cancer angiogenesis. Current Cancer Drug Targets, 7(8), 743–758.

    PubMed  CAS  Google Scholar 

  58. Polette, M., et al. (2004). Tumour invasion and matrix metalloproteinases. Critical Reviews in Oncology Hematology, 49, 179–186.

    Google Scholar 

  59. Raza, S. L., & Cornelius, L. A. (2000). Matrix metalloproteinases: pro- and anti-angiogenic activities. Journal of Investigative Dermatology Symposium Proceeding, 5, 47–54.

    CAS  Google Scholar 

  60. Lizarraga, F., et al. (2005). Tissue inhibitor of metalloproteinases-4 is expressed in cervical cancer patients. Anticancer Research, 25, 623–627.

    PubMed  CAS  Google Scholar 

  61. Zhang, Y., et al. (2008). Adenovirus carrying TIMP-3: a potential tool for cervical cancer treatment. Gynecologic Oncology, 108(1), 234–240.

    PubMed  CAS  Google Scholar 

  62. Davidson, B., et al. (1999). MMP-2 and TIMP-2 expression correlates with poor prognosis in cervical carcinoma—a clinicopathologic study using immunohistochemistry and mRNA in situ hybridization. Gynecologic Oncology, 73(3), 372–382.

    PubMed  CAS  Google Scholar 

  63. Zhai, Y., et al. (2005). Expression of membrane type 1 matrix metalloproteinase is associated with cervical carcinoma progression and invasion. Cancer Research, 65(15), 6543–6550.

    PubMed  CAS  Google Scholar 

  64. Yaldizl, M., et al. (2005). Expression of E-cadherin in squamous cell carcinomas of the cervix with correlations to clinicopathological features. European Journal of Gynaecologic Oncology, 26, 95–98.

    CAS  Google Scholar 

  65. Kaplanis, K., et al. (2005). E-cadherin expression during progression of squamous intraepithelial lesions in the uterine cervix. European Journal of Gynaecologic Oncology, 26(6), 608–610.

    CAS  Google Scholar 

  66. Van Aarsen, L. A., et al. (2008). Antibody-mediated blockade of integrin alpha v beta 6 inhibits tumor progression in vivo by a transforming growth factor-beta-regulated mechanism. Cancer Research, 68(2), 561–570.

    PubMed  Google Scholar 

  67. Hazelbag, S., et al. (2007). Overexpression of the alpha v beta 6 integrin in cervical squamous cell carcinoma is a prognostic factor for decreased survival. Journal of Pathology, 212(3), 316–324.

    PubMed  CAS  Google Scholar 

  68. Hazelbag, S., et al. (2004). Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer. International Journal of Cancer, 112, 1020–1028.

    CAS  Google Scholar 

  69. Bouda, J., et al. (2005). CD44v6 as a prognostic factor in cervical carcinoma FIGO stage IB. Anticancer Research, 25, 617–622.

    PubMed  CAS  Google Scholar 

  70. Speiser, P., et al. (1997). CD44 is an independent prognostic factor in early-stage cervical cancer. International Journal of Cancer, 74(2), 185–188.

    CAS  Google Scholar 

  71. Costa, S., et al. (2001). CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma. Gynecologic Oncology, 80, 67–73.

    PubMed  CAS  Google Scholar 

  72. Beskow, C., et al. (2006). Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer. British Journal of Cancer, 94(11), 1683–1689.

    PubMed  CAS  Google Scholar 

  73. Lee, J. M., & Bernstein, A. (1995). Apoptosis, cancer and the p53 tumour suppressor gene. Cancer Metastasis Reviews, 14(2), 149–161.

    PubMed  CAS  Google Scholar 

  74. Cuddihy, A. R., & Bristow, R. G. (2004). The p53 protein family and radiation sensitivity: Yes or no? Cancer Metastasis Reviews, 23(3–4), 237–257.

    PubMed  CAS  Google Scholar 

  75. Alfsen, G. C., et al. (2003). The prognostic impact of cyclin dependent kinase inhibitors p21WAF1, p27Kip1, and p16INK4/MTS1 in adenocarcinomas of the uterine cervix: an immunohistochemical evaluation of expression patterns in population-based material from 142 patients with international federation of gynecology and obstetrics stage I and II adenocarcinoma. Cancer, 98(9), 1880–1889.

    PubMed  Google Scholar 

  76. Wootipoom, V., et al. (2004). Prognostic significance of Bax, Bcl-2, and p53 expressions in cervical squamous cell carcinoma treated by radiotherapy. Gynecologic Oncology, 94(3), 636–642.

    PubMed  CAS  Google Scholar 

  77. Zhou, J. H., et al. (2006). Fas-mediated pathway and apoptosis in normal cervix, cervical intraepithelial neoplasia and cervical squamous cancer. Oncology Reports, 16(2), 307–311.

    PubMed  CAS  Google Scholar 

  78. Knox, P. G., et al. (2003). Inhibition of metalloproteinase cleavage enhances the cytotoxicity of Fas ligand. Journal of Immunology, 170(2), 677–685.

    CAS  Google Scholar 

  79. Mora, N., Rosales, R., & Rosales, C. (2007). R-Ras promotes metastasis of cervical cancer epithelial cells. Cancer Immunology, Immunotherapy, 56(4), 535–544.

    PubMed  CAS  Google Scholar 

  80. Rincón-Arano, H., et al. (2003). R-Ras promotes tumor growth of cervical epithelial cells. Cancer, 97(3), 575–585.

    PubMed  Google Scholar 

  81. Rotblat, B., et al. (2008). The ras inhibitor farnesylthiosalicylic Acid (salirasib) disrupts the spatiotemporal localization of active ras: a potential treatment for cancer. Methods in Enzymology, 439, 467–489.

    PubMed  CAS  Google Scholar 

  82. Oka, K., Suzuki, Y., & Nakano, T. (2000). Expression of p27 and p53 in cervical squamous cell carcinoma patients treated with radiotherapy alone: radiotherapeutic effect and prognosis. Cancer, 88(12), 2766–2773.

    PubMed  CAS  Google Scholar 

  83. Suzuki, Y., et al. (2004). Immunohistochemical study of cell cycle-associated proteins in adenocarcinoma of the uterine cervix treated with radiotherapy alone: p53 status has a strong impact on prognosis. International Journal of Radiation Oncology Biology Physics, 60, 231–236.

    CAS  Google Scholar 

  84. Kim, J. Y., et al. (2007). Clinical significance of p27 and Skp2 protein expression in uterine cervical neoplasm. International Journal of Gynecological Pathology, 26(3), 242–247.

    PubMed  Google Scholar 

  85. Wakatsuki, M., et al. (2008). p73 Protein Expression Correlates With Radiation-Induced Apoptosis in the Lack of p53 Response to Radiation Therapy for Cervical Cancer. International Journal of Radiation Oncology Biology Physics, 70(4), 1189–1194.

    CAS  Google Scholar 

  86. Santucci, M. A., et al. (2000). Radiation-induced gadd45 expression correlates with clinical response to radiotherapy of cervical carcinoma. International Journal of Radiation Oncology Biology Physics, 46(2), 411–416.

    CAS  Google Scholar 

  87. Cerciello, F., et al. (2005). G2/M cell cycle checkpoint is functional in cervical cancer patients after initiation of external beam radiotherapy. International Journal of Radiation Oncology Biology Physics, 62(5), 1390–1398.

    Google Scholar 

  88. Lee, J. S., et al. (2006). Expression of PTEN in the progression of cervical neoplasia and its relation to tumor behavior and angiogenesis in invasive squamous cell carcinoma. Journal of Surgical Oncology, 93, 233–240.

    PubMed  CAS  Google Scholar 

  89. Cheung, T. H., et al. (2004). Epigenetic and genetic alternation of PTEN in cervical neoplasm. Gynecologic Oncology, 93(3), 621–627.

    PubMed  CAS  Google Scholar 

  90. Nair, A., et al. (2003). NF-kappaB is constitutively activated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the human uterine cervix. Oncogene, 22(1), 50–58.

    PubMed  CAS  Google Scholar 

  91. Han, S., et al. (2008). PPAR{beta}/{delta}agonist stimulates human lung carcinoma cell growth through inhibition of PTEN expression: the involvement of PI3-K and NF-{kappa}B signals. American Journal of Physiology- Lung Cell and Molecular Physiology, 294, L1238–L1249.

    CAS  Google Scholar 

  92. Köster, F., et al. (2007). Correlation of DNA mismatch repair protein hMSH2 immunohistochemistry with p53 and apoptosis in cervical carcinoma. Anticancer Research, 27(1A), 63–68.

    PubMed  Google Scholar 

  93. Wilson, C. R., et al. (2000). Expression of Ku70 correlates with survival in carcinoma of the cervix. British Journal of Cancer, 83(12), 1702–1706.

    PubMed  CAS  Google Scholar 

  94. Ayene, I. S., Ford, L. P., & Koch, C. J. (2005). Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and gamma radiation. Molecular Cancer Therapeutics, 4(4), 529–536.

    PubMed  CAS  Google Scholar 

  95. Harima, Y., et al. (2003). Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival. American Journal of Clinical Oncology, 26(4), 80–85.

    Google Scholar 

  96. Ishikawa, M., et al. (2006). Overexpression of p16 INK4a as an indicator for human papillomavirus oncogenic activity in cervical squamous neoplasia. International Journal of Gynecological Cancer, 16(1), 347–353.

    PubMed  CAS  Google Scholar 

  97. Martin, C. M., et al. (2007). Gene discovery in cervical cancer: towards diagnostic and therapeutic biomarkers. Molecular Diagnosis & Therapies, 11(5), 277–290.

    CAS  Google Scholar 

  98. Madrigal, M., et al. (1997). In vitro antigene therapy targeting HPV-16 E6 and E7 in cervical carcinoma. Gynecological Oncology, 64(1), 18–25.

    CAS  Google Scholar 

  99. Sima, N., et al. (2007). Antisense targeting human papillomavirus type 16 E6 and E7 genes contributes to apoptosis and senescence in SiHa cervical carcinoma cells. Gynecological Oncology, 106(2), 299–304.

    CAS  Google Scholar 

  100. Tan, T. M., & Ting, R. C. (1995). In vitro and in vivo inhibition of human papillomavirus type 16 E6 and E7 genes. Cancer Research, 55(20), 4599–4605.

    PubMed  CAS  Google Scholar 

  101. de Wilde, J., et al. (2008). Gene expression profiling to identify markers associated with deregulated hTERT in HPV-transformed keratinocytes and cervical cancer. International Journal of Cancer, 122(4), 877–888.

    Google Scholar 

  102. Amine, A., et al. (2006). Cidofovir administered with radiation displays an antiangiogenic effect mediated by E6 inhibition and subsequent TP53-dependent VEGF repression in HPV18+ cell lines. Radiation Research, 166(4), 600–610.

    PubMed  CAS  Google Scholar 

  103. Abdulkarim, B., et al. (2002). Antiviral agent Cidofovir restores p53 function and enhances the radiosensitivity in HPV-associated cancers. Oncogene, 21(15), 2334–2346.

    PubMed  CAS  Google Scholar 

  104. Harima, Y., et al. (1999). Genetic alterations on chromosome 17p associated with response to radiotherapy in bulky cervical cancer. British Journal of Cancer, 81(1), 108–113.

    PubMed  CAS  Google Scholar 

  105. Harima, Y., et al. (2000). Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer. Clinical Cancer Research, 6(3), 1079–1085.

    PubMed  CAS  Google Scholar 

  106. Kozlowski, L., et al. (2006). Loss of heterozygosity on chromosomes 2p, 3p, 18q21.3 and 11p15.5 as a poor prognostic factor in stage II and III (FIGO) cervical cancer treated by radiotherapy. Neoplasma, 53(5), 440–443.

    PubMed  CAS  Google Scholar 

  107. Rao, P. H., et al. (2004). Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma. BioMed Central Cancer, 4, 5.

    PubMed  Google Scholar 

  108. Terra, A. P., et al. (2007). Aberrant promoter methylation can be useful as a marker of recurrent disease in patients with cervical intraepithelial neoplasia grade III. Tumori, 93(6), 572–579.

    PubMed  CAS  Google Scholar 

  109. Lindström, A. K., et al. (2007). Predicting the outcome of squamous cell carcinoma of the uterine cervix using combinations of individual tumor marker expressions. Anticancer Research, 27(3B), 1609–1615.

    PubMed  Google Scholar 

  110. Narayan, G., et al. (2007). Gene dosage alterations revealed by cDNA microarray analysis in cervical cancer: identification of candidate amplified and overexpressed genes. Genes Chromosomes Cancer, 46(4), 373–384.

    PubMed  CAS  Google Scholar 

  111. Achary, M. P., et al. (2000). Cell lines from the same cervical carcinoma but with different radiosensitivities exhibit different cDNA microarray patterns of gene expression. Cytogenetics and Cell Genetics, 91(1–4), 39–43.

    PubMed  CAS  Google Scholar 

  112. Chao, A., et al. (2006). Molecular characterization of adenocarcinoma and squamous carcinoma of the uterine cervix using microarray analysis of gene expression. International Journal of Cancer, 119(1), 91–98.

    CAS  Google Scholar 

  113. Chen, Y., et al. (2003). Identification of cervical cancer markers by cDNA and tissue microarrays. Cancer Research, 63(8), 1927–1935.

    PubMed  CAS  Google Scholar 

  114. Gaffney, D. K., et al. (2005). Feasibility of RNA collection for micro-array gene expression analysis in the treatment of cervical carcinoma: a scientific correlate of RTOG C-0128. Gynecological Oncology, 97(2), 607–611.

    CAS  Google Scholar 

  115. Collis, S. J., & De Weese, T. L. (2004). Enhanced radiation response through directed molecular targeting approaches. Cancer Metastasis Reviews, 23(3–4), 277–292.

    PubMed  CAS  Google Scholar 

  116. Gu, W., et al. (2006). Inhibition of cervical cancer cell growth in vitro and in vivo with lentiviral-vector delivered short hairpin RNA targeting human papillomavirus E6 and E7 oncogenes. Cancer Gene Therapy, 13(11), 1023–1032.

    PubMed  CAS  Google Scholar 

  117. Moeller, B. J., Richardson, R. A., & Dewhirst, M. W. (2007). Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Reviews, 26(2), 241–248.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiotherapy, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805, Villejuif, France

    Nicolas Magné, Cyrus Chargari, Eric Deutsch, Mitra Ghalibafian, Jean Bourhis & Christine Haie-Meder

  2. Department of Radio Oncology, Institut Jules Bordet, Brussels, Belgium

    Pierre Castadot

Authors
  1. Nicolas Magné
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cyrus Chargari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric Deutsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pierre Castadot
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mitra Ghalibafian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean Bourhis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christine Haie-Meder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicolas Magné.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magné, N., Chargari, C., Deutsch, E. et al. Molecular profiling of uterine cervix carcinoma: an overview with a special focus on rationally designed target-based anticancer agents. Cancer Metastasis Rev 27, 737–750 (2008). https://doi.org/10.1007/s10555-008-9162-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-008-9162-7

Keywords

Search

Navigation