Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and splitting, but processes such as coalescent angiogenesis, vessel elongation and vessel cooption also play a role. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise. The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease.
Vascular endothelial growth factor, originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis and angiogenesis.
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.
Erlotinib, sold under the brand name Tarceva among others, is a medication used to treat non-small cell lung cancer (NSCLC) and pancreatic cancer. Specifically it is used for NSCLC with mutations in the epidermal growth factor receptor (EGFR) — either an exon 19 deletion (del19) or exon 21 (L858R) substitution mutation — which has spread to other parts of the body. It is taken by mouth.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from preexisting blood vessels. Angiogenesis proceeds through sprouting, endothelial cell migration, proliferation, and vessel destabilization and stabilization. They are responsible for assembling and disassembling the endothelial lining of blood vessels. Angiopoietin cytokines are involved with controlling microvascular permeability, vasodilation, and vasoconstriction by signaling smooth muscle cells surrounding vessels. There are now four identified angiopoietins: ANGPT1, ANGPT2, ANGPTL3, ANGPT4.
Matuzumab is a humanized monoclonal antibody for the treatment of cancer. It binds to the epidermal growth factor receptor (EGFR) with high affinity. The mouse monoclonal antibody (mAb425) from which matuzumab was developed at the Wistar Institute in Philadelphia, Pennsylvania
Semaxanib is a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic. It is an experimental stage drug, not licensed for use on human patients outside clinical trials. Semaxanib is a potent and selective synthetic inhibitor of the Flk-1/KDR vascular endothelial growth factor (VEGF) receptor tyrosine kinase. It targets the VEGF pathway, and both in vivo and in vitro studies have demonstrated antiangiogenic potential.
Cediranib is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.
VEGF receptors (VEGFRs) are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Depending on alternative splicing, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR).
Axitinib, sold under the brand name Inlyta, is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types.
Vascular endothelial growth factor A (VEGF-A) is a protein that in humans is encoded by the VEGFA gene.
Lenvatinib, sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases.
Apatinib, also known as rivoceranib, is a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis in cancer cells; specifically, apatinib inhibits VEGF-mediated endothelial cell migration and proliferation thus blocking new blood vessel formation in tumor tissue. This agent also mildly inhibits c-Kit and c-SRC tyrosine kinases.
A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis.
Angiokinase inhibitors are a new therapeutic target for the management of cancer. They inhibit tumour angiogenesis, one of the key processes leading to invasion and metastasis of solid tumours, by targeting receptor tyrosine kinases. Examples include nintedanib, afatinib and motesanib.
Foretinib is an experimental drug candidate for the treatment of cancer. It was discovered by Exelixis and is under development by GlaxoSmithKline. About 10 Phase II clinical trials have been run. As of October 2015 it appears development has been discontinued.
Brivanib alaninate (INN/USAN) also known as BMS-582664 is an investigational, anti-tumorigenic drug for oral administration. The drug is being developed by Bristol-Myers Squibb for the treatment of hepatocellular carcinoma or HCC, the most common type of liver cancer. Brivanib is no longer in active development.
Growth factor receptor inhibitors are drugs that target the growth factor receptors of cells. They interfere with binding of the growth factor to the corresponding growth factor receptors, impeding cell growth and are used medically to treat cancer.
VEGFR-2 inhibitor, also known as kinase insert domain receptor(KDR) inhibitor, are tyrosine kinase receptor inhibitors that reduce angiogenesis or lymphangiogenesis, leading to anticancer activity. Generally they are small, synthesised molecules that bind competitively to the ATP-site of the tyrosine kinase domain. VEGFR-2 selective inhibitor can interrupt multiple signaling pathways involved in tumor, including proliferation, metastasis and angiogenesis.
