Targeting angiogenesis in endometrial cancer - new agents for tailored treatments

Abstract

Introduction: Endometrial carcinoma represents the most frequent gynecologic tumor in developed countries. The majority of women presents with low-grade tumors but a significant subset of women experience recurrence and do not survive their disease. Patients with stage III/ IV or recurrent endometrial cancer have a poor prognosis. Identification of active and tolerable new targeted agents versus specific molecular targets is a priority objective. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer and in particular endometrial cancer.

Areas covered: In this review, the authors highlight the main angiogenetic molecular pathways and the anti-angiogenic agents in Phase II clinical trials for endometrial cancer treatment. The authors focus on reports from recent years on angiogenesis inhibitors used in endometrial cancer, including anti- vascular endothelial growth factor (VEGF) monoclonal antibodies (bevacizumab and aflibercept), mammalian target of rapamycin inhibitors (mTORi) (everolimus, temsirolimus and ridaforolimus), PI3 K inhibitors (BKM120), tyrosine kinase inhibitors (brivanib, sunitinib, dovitinib and nintedanib) and thalidomide.

Expert opinion: These anti-angiogenic drugs, while used either alone or in combination with chemotherapy, have presented mixed results in treating endometrial cancer patients. Challenges for the future include the identification of new pathways, early identification and overcoming resistance and the use of these molecules in combination with old and new chemotherapeutic and targeted agents.

Keywords:

• angiogenesis
• endometrial cancer
• monoclonal antibodies
• small molecules
• target therapies

Article highlights

• Endometrial carcinoma represents the most frequent gynecologic tumor in developed countries, with an incidence of 15 – 20/100,000 cases for year.

• Particularly, the 5-year survival for patients at stage I is 85 – 91%, and unfortunately the disease-related death rate in patients at FIGO I-IIA stage is still high, ranging from 5 to 15%.

• Patients with stage III/IV or recurrent disease have still today a poor prognosis and currently they are treated with hormonal therapy, chemotherapy or radiotherapy, frequently with palliative intent.

• Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer, included endometrial cancer.

• Anti-angiogenic drugs presented interesting but conflicting results in treating patients with advanced and relapsed endometrial cancer.

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