Abstract
Uterine cervical cancer is the most common gynecologic malignancy in women worldwide in both prevalence and mortality. In 2012 an estimated 527,600 cancer cases and 265,700 related deaths were registered. Over 99% of cervical carcinomas are caused by the human papillomavirus (HPV).Different components of the HPV, especially E6 and E7 oncoproteins, are responsible for the early transformation of the stratified squamous epithelia of the cervix and subsequent carcinogenesis. Concurrently, these translated oncoproteins promote angiogenesis in cervical cancer. The unique characteristic of HPV-driven angiogenesis is the early onset of the angiogenic switch in carcinogenesis. As this mechanism underlies the vascular endothelial growth factor (VEGF-) pathway, anti-angiogenic therapeutics targeting VEGF or its transmembrane tyrosine kinase receptor are of increasing interest.
Until 2014 bevacizumab was investigated in a phase III trial and proved significant efficacy without simultaneous alarming toxicity. Bevacizumab was approved by the US Food and Drug Administration in the therapy of persistent, recurrent, or metastatic cervical cancer in combination with cisplatin or topotecan and paclitaxel. This outstanding innovation paved the way for further anti-angiogenic drugs. Cediranib, pazopanib, and sunitinib have recently undergone phase I and II trials with variable success. However, with the introduction of Bevacizumab to cervical cancer therapy and the knowledge that angiogenic mechanisms appear much earlier in cervical cancer than most other entities because of HPV infection, cervical cancer therapy has taken a new direction.
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References
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Erbes, T., Farthmann, J., Berner, K. (2018). The Value of Anti-angiogenics in Cervical Cancer Therapy. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_26-1
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