Antiangiogenic therapy in oncology: current status and future directions

Gordon C Jayson; Robert Kerbel; Lee M Ellis; Adrian L Harris

doi:10.1016/S0140-6736(15)01088-0

Antiangiogenic therapy in oncology: current status and future directions

Lancet. 2016 Jul 30;388(10043):518-29. doi: 10.1016/S0140-6736(15)01088-0. Epub 2016 Feb 5.

Authors

Gordon C Jayson¹, Robert Kerbel², Lee M Ellis³, Adrian L Harris⁴

Affiliations

¹ Institute of Cancer Sciences and Christie Hospital, University of Manchester, Manchester, UK. Electronic address: gordon.jayson@ics.manchester.ac.uk.
² Biological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
³ Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Department of Medical Oncology, Churchill Hospital, University of Oxford, Oxford, UK.

PMID: 26853587
DOI: 10.1016/S0140-6736(15)01088-0

Abstract

Angiogenesis, the formation of new blood vessels from pre-existing vessels, has been validated as a target in several tumour types through randomised trials, incorporating vascular endothelial growth factor (VEGF) pathway inhibitors into the therapeutic armoury. Although some tumours such as renal cell carcinoma, ovarian and cervical cancers, and pancreatic neuroendocrine tumours are sensitive to these drugs, others such as prostate cancer, pancreatic adenocarcinoma, and melanoma are resistant. Even when drugs have yielded significant results, improvements in progression-free survival, and, in some cases, overall survival, are modest. Thus, a crucial issue in development of these drugs is the search for predictive biomarkers-tests that predict which patients will, and will not, benefit before initiation of therapy. Development of biomarkers is important because of the need to balance efficacy, toxicity, and cost. Novel combinations of these drugs with other antiangiogenics or other classes of drugs are being developed, and the appreciation that these drugs have immunomodulatory and other modes of action will lead to combination regimens that capitalise on these newly understood mechanisms.

Publication types

Review

MeSH terms

Angiogenesis Inhibitors / pharmacology
Angiogenesis Inhibitors / therapeutic use*
Angiopoietin-1 / antagonists & inhibitors
Biomarkers, Tumor / blood
Biomarkers, Tumor / metabolism*
Disease-Free Survival
Drug Resistance, Neoplasm
Female
Humans
Molecular Targeted Therapy* / methods
Neoplasms / blood supply
Neoplasms / drug therapy*
Neoplasms / metabolism
Neovascularization, Pathologic / drug therapy*
Neovascularization, Pathologic / prevention & control
Niacinamide / analogs & derivatives
Niacinamide / therapeutic use
Phenylurea Compounds / therapeutic use
Phthalazines / therapeutic use
Piperazines / therapeutic use
Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
Protein Kinase Inhibitors / therapeutic use
Quinazolines / therapeutic use
Quinolines / therapeutic use
Receptor, TIE-2 / antagonists & inhibitors
Signal Transduction / drug effects
Sorafenib
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Vascular Endothelial Growth Factor A / metabolism

Substances

ANGPT1 protein, human
Angiogenesis Inhibitors
Angiopoietin-1
Biomarkers, Tumor
Phenylurea Compounds
Phthalazines
Piperazines
Poly(ADP-ribose) Polymerase Inhibitors
Protein Kinase Inhibitors
Quinazolines
Quinolines
VEGFA protein, human
Vascular Endothelial Growth Factor A
Niacinamide
Sorafenib
Receptor, TIE-2
lenvatinib
cediranib
olaparib

Abstract

Publication types

MeSH terms

Substances

Grants and funding