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Cancer needs a good blood supply to bring food and oxygen and remove waste products. In order to grow larger than one or two mm a tumour needs its own blood supply. Some cancers produce VEGF (vascular endothelial growth factor) which attaches to receptors on the wall of the blood vessel and triggers blood vessel growth. Angiogenesis means the growth of new blood vessels. Stopping angiogenesis can stop tumours growing and can shrink them. Some targeted therapies aim to do this.
Tyrosine kinase inhibitors (TKI’s) block the VEGF receptor on the blood vessel; acting to stop the blood vessel growth signal. TKI’s include pazopanib, sunitinib, axitinib and sorafenib.
mTOR inhibitors. mTOR is a type of protein called a kinase protein. It can make cells produce chemicals such as cyclins that trigger cell growth. It may also make cells produce proteins that trigger the development of new blood vessels. Inhibiting this pathway may reduce cell growth and blood vessel formation. mTOR inhibitors include everolimus and temsirolimus.
The Monoclonal antibody bevacizumab blocks VEGF and has an anti-angiogenic action (stops blood vessel formation).
Targeted therapies that have been used for kidney cancer include pazopanib, sunitinib, axitinib, everolimus, temsirolimus, sorafenib and bevacizumab. However, not all of these drugs are routinely used or funded within the NHS. NICE only recommend pazopanib and sunitinib as a first-line treatment of advanced kidney cancer. Axitinib is the only drug recommended for use as a second-line treatment after failure of prior systemic treatment (Nivolumab is also recommended as a second line treatment option. More details about this drug can be found in the immunotherapy/monoclonal antibody section).
For more details on their effectiveness, side-effects, mechanism of action, dosage and safety, please view the downloadable targeted therapy chart. Hopefully the information provided will help you discuss treatment options with your doctor.
mTOR inibitors include everolimus and temsirolimus; neither of these are recommended by NICE.
mTOR is a protein kinase (enzyme which alters other proteins in the cell) and they are important in cellular signalling pathways which increase cell growth and blood vessel formation. mTOR inihibitors act to stop the cancer cells from replicating, growing and supplying themselves with a blood supply.
More details on mTOR safety, side-effects, effectiveness and dosage are available on the targeted therapies downloadable chart.
Tyrosine Kinase Inhibitors
Sunitinib and pazopanib are tyrosine kinase inhibitors that are currently recommended by NICE for the first-line treatment of advanced kidney cancer. Axitinib is a second-line treatment which is recommended by NICE after prior failure of systemic treatment. Sorafenib is also a tyrosine kinase inhibitor but is not recommended for use by NICE.
These drugs block a variety of tyrosine kinases (enzymes) within a cancer cell. They interfere with the signaling pathways that the cancer cells depend on for creating a blood supply and increasing in number.
The targeted therapies downloadable chart provides more details about tyrosine kinase inhibitors.
VEGF-A Inhibitor (monoclonal antibody)
Bevacizumab is a monoclonal antibody which blocks the VEGF receptor on blood vessels. Blocking these receptors stops the blood vessel from growing (angiogenesis is stopped). The tumour will not be able to grow new blood vessels to support its growth and hopefully it will not increase in size and may shrink. This drug could be classed within 2 different targeted therapy groups; drugs that stop blood vessel formation and monoclonal antibody group.
Bevacizumab is not currently recommended by NICE.
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