| As seen in the above figure, kidney cancer cells produce VEGF, which causes blood vessels to grow to the tumor. As blood vessels grow into the tumor, the tumor cells receive the nutrients they require to survive, which further encourages their growth. When VEGF is inhibited, new blood vessels do not grow, and the kidney cancer cells starve and eventually die.
Our expanding understanding of the biology of kidney cancer during the last few years resulted in the identification of a number of new possible targets for the treatment of advanced RCC. The introduction of these new medications will likely dramatically improve the prognosis for patients with metastatic kidney cancer and, for the first time, offers a wide range of medication treatment options that previously did not exist.
The most common type of kidney cancer is known as conventional or clear cell kidney cancer. Approximately 80% of all kidney cancers are classified as conventional kidney cancer. In recent years, scientist have related conventional kidney cancer to changes in a gene named von Hippel–Lindau (VHL). Conventional kidney cancer develops as a consequence of VHL gene loss which results in an increased amount of a protein known as hypoxia inducible factor (HIF). It is HIF that leads to highly vascular tumors. Overexpression of HIF is also caused by stimulation of a receptor called the mammalian target of rapamycin (mTOR). mTOR is a key component of signaling pathways inside our cells, and mTOR involved in cell growth processes. The blocking of pathways that create blood vessels to feed kidney cancer (including mTOR) was the primary objective behind the development of new targeted agents for advanced kidney cancer. Since December of 2005, 5 targeted agents have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced kidney cancer: Sorafenib and Sunitinib are medications which can be taken by mouth and have been shown to directly block the development of blood vessels which feed kidney cancer cells (these medicines block vascular endothelial growth factor receptors -2 and -3 (VEGFR-2, VEGFR-3) and platelet-derived growth factor receptor beta (PDGFR-beta). Temsirolimus and everolimus are medications which block the mTOR pathway described above. Bevacizumab a medicine which is actually made like a component of the human immune system (a monoclonal antibody). Bevacizumab specifically targets the chemical VEGF (see figure below).
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Figure: Mechanism of action of targeted therapies in renal cell carcinoma. |
Sorafenib and Sunitinib are the two tyrosine kinase inhibitors (TKIs) that are approved for the treatment of kidney cancer. Sorafenib and Sunitinib are taken by mouth and then circulate through the body until they bind receptor tyrosine kinases located on the cell surface. When Sorafenib and Sunitinib bind to the receptor, they block the signal that the receptor sends. The blocking of this growth and development signal in kidney cancer cells results in shrinkage. Sorafenib and Sunitinib are similar in their mode of action, and therefore they share some common characteristics. |
