Abstract
Angiogenesis is a hallmark of tumor development and metastasis and is now a validated target for cancer treatment. However, the overall benefits of antiangiogenic drugs from the perspective of impacting survival have left much to desire, endorsing a need for developing more effective therapeutic regimens, e.g., combining antiangiogenic drugs with established chemotherapeutic drugs. In this review, we discuss progress in the synergistic design of antiangiogenic agents in combination with targeted therapies. Targeted cancer therapies include monoclonal antibodies and small-molecule inhibitors that have significantly changed the treatment of cancer over the past years. We focus on antiangiogenic agents combined with targeted therapies inhibiting the epidermal growth factor receptor (EGFR) pathway and the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target of rapamycin) pathway and inhibiting immune checkpoint receptors, such as CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) and PD1/PDL1 (programmed cell death protein 1/PD1 ligand). Of note, not always, encouraging preclinical data particularly of VEGF and EGFR inhibitor combinations did translate into the clinics. In addition, we highlight the rapidly developing field of VEGF-based humanized tri-specific nanobodies and novel VEGFR2-targeted antibody-based fusion proteins, potentially providing a new inspiration for antitumor treatment.
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Zirlik, K., Duyster, J. (2017). Combination of Antiangiogenics and Other Targeted Therapies. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_14-1
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