Crosstalk between HER2 signaling and angiogenesis in breast cancer: Molecular basis, clinical applications and challenges

PURPOSE OF REVIEW: Angiogenesis is an essential hallmark of cancer. Targeting angiogenesis has proven its efficacy in the modern therapeutic paradigm. HER2 positive breast cancer, in particular, is a challenging disease in which resistance to standard therapy has been attributed to parallel and downstream signaling cascades including angiogenesis. This review explores the molecular mechanisms underlying crosstalk between HER2 signaling and angiogenesis. It highlights the role of angiogenesis in the emerging resistance to anti-HER2 therapy. It surveys the current repertoire of clinical trials involving use of combination of anti-HER2 and antiangiogenic therapies. Finally, it entertains the hopes and challenges posed by this novel therapeutic approach. RECENT FINDINGS: HER2 signaling upregulates angiogenesis at different levels and by different mechanisms. A large number of clinical trials were conducted in attempt to exploit the potential benefit of the combination. Results of early phase trials were promising. However, in the late phase clinical trials, the AVEREL trial did not demonstrate a consistent benefit for bevacizumab in the HER2 positive breast cancer patient population. The BETH trial is ongoing and recruiting patients. Safety issues regarding cardiovascular toxicity of the combination have been already raised. Negative experience of dual EGFR and VEGF targeting in colon cancer cannot be overlooked. SUMMARY: Angiogenesis and HER2 signaling are closely related at the molecular level. Appraisal of efficacy of antiangiogenic therapies requires revisit of the current literature as well as following the results of ongoing trials. © 2013 Wolters Kluwer HealthSCOPUS: re.jinfo:eu-repo/semantics/publishe

Is VEGF a predictive biomarker to anti-angiogenic therapy?

Tumor growth and metastasis are dependent on angiogenesis. Inhibiting angiogenesis has therapeutic potentials for treating cancer. Researchers have identified many of the pathways involved in angiogenesis and proposed selective targeted strategies. A high probability of benefit is desirable to justify the choice of anti-angiogenic therapy from an ever-expanding list of expensive new anticancer agents. However, biomarkers of response to anti-angiogenic agents are inconclusive for predicting benefit from these drugs. This paper reviews the most important biomarker of angiogenesis, namely VEGF, in relation to its expression in cancer and the treatment of these cancers through targeting VEGF and its pathways. © 2010 Elsevier Ireland Ltd.SCOPUS: re.jinfo:eu-repo/semantics/publishe