Current Angiogenesis (Discontinued) - Volume 3, Issue 2, 2014

Ovarian cancer has a poor prognosis even after a complete resection and a platinum adjuvant chemotherapy because of its high rate of relapses. Clinical research has shown the role of angiogenesis in the development and progression of ovarian carcinoma. Several factors are involved, specially the VEGF. Bevacizumab is a humanized anti-VEGF antibody that was approved by the European Medicines Agency in first line for the treatments of advanced epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer. It has to be combined with carboplatin and paclitaxel followed by maintenance therapy with bevacizumab alone. Bevacizumab has also been approved by EMA for the treatment of platinum-sensitive ovarian cancer recurrence in combination with carboplatin and gemcitabine. This literature review aims to provide updates about angiogenesis in ovarian cancer, pro-and anti-angiogenic factors that regulate angiogenesis, and lists new anti-angiogenic therapies in different phases of clinical development that aim to improve survival in patients with ovarian cancer.

Non-small cell lung cancer is the first cause of cancer mortality in the world. Despite therapeutic improvements in the last decade, the survival rate has barely changed. Recent advances in the understanding of the signal pathways suggest an essential role of angiogenesis in the pathogenesis of NSCLC. Bevacizumab, a monoclonal antibody against circulating vascular endothelial growth factor (VEGF), is the first approved antiangiogenic drug treating NSCLC. Many other anti-angiogenic agents are under development, including VEGF Trap and tyrosine kinase inhibitors with encouraging results, particularly triple angiokinase inhibitors, which inhibit VEGF, platelet derived growth factor (PDGF) and fibroblast derived growth factor FGF. These agents may improve the therapeutic outcomes for patients with NSCLC. Nevertheless, there is a need to identify appropriate biomarkers to select patients who are benefiting from anti-angiogenesis therapy.

Angiogenesis is an important step in breast cancer (BC) growth and progression. Targeting angiogenesis was the most interesting by developed strategy in the treatment of HER2-negative BC. Bevacizumab is a monoclonal humanized antibody targeting the vascular endothelial growth factor (VEGF) the most potent factor implicated in tumor angiogenesis. It is the most developed targeted agent in HER2-negative MBC and showed the most interesting results in combination with chemotherapy. Currently, bevacizumab is the only approved targeted therapy (in Europe only) in the first line treatment of HER2-negative metastatic BC in combination with weekly paclitaxel. The aim of the present paper is to review the role of anti-angiogenic agents (targeted agents only) in the treatment of HER2-negative metastatic BC.

Angiogenesis is a key issue in the carcinogenesis progression. The development of anti-angiogenic targeted therapies has made significant progress over the last decade. Targeting angiogenesis is considered as a part of the treatment of metastatic colorectal cancer. Less data is available for the other gastrointestinal cancers. The objective of this article is to provide a review of the angiogenesis targeting drugs evaluated in gastrointestinal non colorectal cancers. The review is focused on the following 5 common gastrointestinal cancers: gastric, pancreatic, neuroendocrine cancers, biliary cancers, and hepatocellular carcinoma.

Angiogenesis is an essential mechanism for tumor development and proliferation. In the last decade, inhibition of this mechanism has shown mostly encouraging results in different types of cancers. Urogenital cancers (Prostate, Bladder, Testis and Kidney) represent approximately 25% of all diagnosed cancers in both sexes and much effort has been made in order to incorporate anti-angiogenic agents in the treatment of these cancers. Inhibition of angiogenesis is the cornerstone of therapy in Renal Cell Carcinoma and has shown somewhat promising results in prostate cancer. However, studies in both Urothelial carcinoma and Germ Cell Tumors remain mostly disappointing. In this paper, we report the landmark trials evaluating anti-angiogenic drugs in uro-genital cancers.

Sarcomas are uncommon malignancies which gather more than 80 different subtypes in the most recent WHO classification. Surgery remains the mainstay for the treatment of localized disease; however, effective treatment of advanced soft tissue sarcoma remains a challenge. Advances in understanding the molecular biology and carcinogenesis of sarcoma have allowed for rapid development of new targeted therapies. In this review we will provide current knowledge on antiangiogenic therapies in non-GIST soft tissue sarcomas. The contribution of angiogenesis to sarcoma development has been documented in preclinical models, and in the clinic. Angiogenesis plays a central role in the growth and dissemination of soft tissue sarcoma and correlates with higher-grade STS and a poorer outcome. Many angiogenesis inhibitors have shown activity in STS and pazopanib an antiangiogenic agent is now available in clinical routine. In this manuscript, we will present the results of preclinical research and clinical trials that have evaluated angiogenesis inhibitors in non GIST soft tissue sarcomas.

Thyroid cancers are characterized by a good prognosis but 10 to 15% of patients progress and become refractory to current therapies. Systemic treatment based on chemotherapy in these settings has shown limited efficacy, with response rates not exceeding 25%. At progression, differentiated thyroid cancer is characterized by a high level of expression of vascular endothelial growth factor (VEGF). This high expression of VEGF is associated with an aggressive tumor behavior and a poor clinical outcome. We will review the recent advances in targeting angiogenesis in the treatment of recurrent and metastatic thyroid carcinoma.

Angiogenesis is a physiological process involved in the maturation and the development of the tissues, allowing a supply of oxygen and nutrients [1]. This process is stimulated in certain pathological conditions, including carcinogenesis. Angiogenesis has long been regarded as an important target in the treatment of cancer. Much progress has been made in identifying factors involved in angiogenesis, as well as treatment options for many cancers, thanks to antiangiogenic therapies [2, 3]. So it appears that angiogenesis has significant mechanistic complexity, resistance and therapeutic exhaust now are practical limits to the development of drugs [4]. Recent studies in several experimental models suggest that both tumor and non-tumor (stromal) cell types may be involved in the reduced responsiveness to the treatments. The current review focuses on mechanisms, which result in dynamic changes occur in the tumor microenvironment in response to antiangiogenic therapy, resulting in drug resistance. These mechanisms include direct selection of clonal cell populations with the ability to rapidly upregulate other proangiogenic channels, an increased capacity for invasion and an intrinsic resistance to hypoxia [5].

The use of anti-angiogenic therapies has revolutionized the treatment of cancer. However, some of these drugs are associated with cardiovascular damage. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. An early detection and personalized management is necessary to screen and treat an increase in blood pressure or symptomatic left ventricular dysfunction. The interruption of treatment is recommended if cardiac manifestations are uncontrolled, unless the expected benefit is greater than the risks. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or oncocardiology.