Antiangiogenics and immunotherapies in cervical cancer: an update and future’s view
- 659 Downloads
Despite availability of primary and secondary prevention measures, cervical cancer (CC) persists as one of the most common cancers among women around the world, and more than 70% of cases are diagnosed at advanced stages. Although significant progress has been made in the treatment of CC, around 15–61% of patients develop a recurrence in lymph nodes or distant sites within the first 2 years of completing treatment and the prognosis for these patients remains poor. During the last decades, in an attempt to improve the outcome in these patients, novel agents as combination therapy that target known dysfunctional molecular pathways have been developed with the most attention to the inhibitors of the angiogenesis process. One therapeutic target is the vascular endothelial growth factor, which has been shown to play a key role in tumor angiogenesis, not only for growth of new tissue but also in tumor proliferation. Bevacizumab is recognized as a potent antiangiogenic agent in ovarian cancer but has also demonstrated encouraging antitumor activity in recurrent CC. Moreover, other antiangiogenic agents were recently under study including: sunitinib, sorafenib, pazopanib, cediranib and nintedanib with interesting preliminary results. Moreover, over the last few years there has been increasing interest in cellular immunotherapy as a strategy to harness the immune system to fight tumors. This article focuses on recent discoveries about antiangiogenic agents and immunotherapies in the treatment of CC highlighting on future’s view.
KeywordsAntiangiogenic therapies Cervical cancer Bevacizumab Pazopanib Immunotherapy Vaccines
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent was not necessary because the study does not involve human participants
- 2.Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer. 2012;136(2015):E359–86.Google Scholar
- 5.Peters WA, Liu PY, Barrett RGW. Cisplatin, 5-fluorouracil plus radiation therapy are superior to radiation therapy as adjunctive therapy in high risk, early stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: report of a phase III inter group study. Presented at Soc Gynecol Oncol 30th annual meeting, San Francisco, CA, 5–9 Feb, 1999; 1999.Google Scholar
- 7.Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999;17(5):1339–48.CrossRefPubMedGoogle Scholar
- 9.Dishe S. Radiotherapy of cervical cancer. Clim Obstet. Gynecol. 12, 203—227. 17 (1985).Google Scholar
- 12.Benedetti-Panici P, Greggi S, Colombo A, Amoroso M, Smaniotto D, Giannarelli D, Amunni G, Raspagliesi F, Zola P, Mangioni C, Landoni F. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. J Clin Oncol. 2002;20(1):179–88.CrossRefPubMedGoogle Scholar
- 13.Rydzewska L, Tierney J, Vale CL, Symonds PR. Neoadjuvant chemotherapy plus surgery versus surgery for cervical cancer. Cochrane Database Syst Rev. 2012. doi: 10.1002/14651858.CD007406.pub3.
- 17.Eddy GL, Bundy BN, Creasman WT, Spirtos NM, Mannel RS, Hannigan E, O’Connor D. Treatment of (“bulky”) stage IB cervical cancer with or without neoadjuvant vincristine and cisplatin prior to radical hysterectomy and pelvic/para-aortic lymphadenectomy: a phase III trial of the gynecologic oncology group. Gynecol Oncol. 2007;106(2):362–9 Epub 2007 May 9.CrossRefPubMedGoogle Scholar
- 19.Chang TC, Lai CH, Hong JH, Hsueh S, Huang KG, Chou HH, Tseng CJ, Tsai CS, Chang JT, Lin CT, Chang HH, Chao PJ, Ng KK, Tang SG, Soong YK. Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. J Clin Oncol. 2000;18(8):1740–7.CrossRefPubMedGoogle Scholar
- 20.Vale Tierney JF, Stewart LA, et al. Chemoradiotherapy for cervical cancer meta-analysis collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J. Clin. Oncol. 2008;26:5802–12.CrossRefGoogle Scholar
- 22.Angioli R, Luvero D, Aloisi A, Capriglione S, Gennari P, Linciano F, Li Destri M, Scaletta G, Montera R, Plotti F. Adjuvant chemotherapy after primary treatments for cervical cancer: a critical point of view and review of the literature. Expert Rev Anticancer Ther. 2014;14(4):431–9.CrossRefPubMedGoogle Scholar
- 23.Angioli R, Plotti F, Aloisi A, Scaletta G, Capriglione S, Luvero D, Fiore L, Terranova C, Montera R, Panici PB. A randomized controlled trial comparing four versus six courses of adjuvant platinum-based chemotherapy in locally advanced cervical cancer patients previously treated with neo-adjuvant chemotherapy plus radical surgery. Gynecol Oncol. 2015;139(3):433–8.CrossRefPubMedGoogle Scholar
- 32.Schefter TE, Winter K, Kwon JS, et al. A phase II study of bevacizumab in combination with definitive radiotherapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma: preliminary results of RTOG 0417. Int J Radiat Oncol Biol Phys. 2012;83(1179–84):28.Google Scholar
- 37.European Medicines Agency (2013). Avastin: summary of product characteristics. http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_Product_Information/human/000582/.
- 41.Penson RT, Huang HQ, Wenzel LB, Monk BJ, Stockman S, Long HJ 3rd, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Method M, Michael H, Tewari KS. Bevacizumab for advanced cervical cancer: patient-reported outcomes of a randomised, phase 3 trial (NRG Oncology-Gynecologic Oncology Group protocol 240). Lancet Oncol. 2015;16(3):301–11.CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Milosevic MF, Townsley CA, Chaudary N, Clarke B, Pintilie M, Fan S, Glicksman R, Haider M, Kim S, MacKay H, Yeung I, Hill RP, Fyles A, Oza AM. Sorafenib increases tumor hypoxia in cervical cancer patients treated with radiation therapy: results of a Phase 1 clinical study. Int J Radiat Oncol Biol Phys. 2016;94(1):111–7.CrossRefPubMedGoogle Scholar
- 55.Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, Moreira ED Jr, Ngan Y, Petersen LK, Lazcano-Ponce E, Pitisuttithum P, Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W, Kjaer SK, Bautista OM, Chan IS, Chen J, Gesser R, Moeller E, Ritter M, Vuocolo S, Luxembourg A, Broad Spectrum HPV. Vaccine Study. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372(8):711–23.CrossRefPubMedGoogle Scholar