As I mentioned in last several blogs, the inhibitor of receptor tyrosine kinase (RTK) is widely used to treat solid tumor such as non-small cell lung cancer (NSCLC), breast cancer, ovarian cancer etc. Now another inhibitor of receptor tyrosine kinase (RTK) is being developed by two pharmaceutical company Aveo and Astellas to treat solid tumor. Tivozanib is now under phase III clinical trial for the treatment of advanced renal cell carcinoma (RCC) based on its good results from phase II clinical trial. Tivozanib is an inhibitor of vascular endothelial growth factor (VEGF). Blood vessel is critical for cancer progression becuase cancer cells needs oxygen and nutrition to keep growth. VEGF is a receptor tyrosine kinase that mediates the growth of blood vessel especially in cancer tissue. Blocking VEGF is to eliminate the supply of tumor growth and thus inhibit the progression of tumor. Although effective, the inhibitor of VEGF still has its limitations. For example, some tumor resist the effect of VEGF inhibitor treatment. Inhibitors of VEGF, together with other receptor tyrosine kinase, are the first choice for treating advance renal cell carcinoma (RCC)[1]. Tivozanib is a novel orally available small molecule and is found to be an effective inhibitor of VEGF. It potentially inhibits all three types of VEGF, therefore maximize its on-target effect and limit its off-target toxicity. Phase II clinical trial showed that tivozanib is well tolerated and significantly prolonged the life of patients with advance renal cell carcinoma. The phase III clinical trial, aim to examine widely the effectiveness and safety of the drug, is now in progress. Soon after, the drug will marketed in both USA and Europe. Epidermal keratinocytes is special tissue that keep differentiation to maintain the metabolism of the skin. The mechanism of the continuous differentiation is still not very clear. That is a very interesting topic because the regulation of differentiation is critical in normal skin tissue. The basal level of epidermis keep differentiation and keep moving up to until the top level of the skin. The regulation of this specific differentiation process is because of the turning on or off specific genes. This process is totally normal in skin, but in other organs, the continuous differentiation is characteristic of the cancer. Apoptosis is program cell death which is induced by harmful environmental signal. Autophagy is a process that cells begin to digest its own compartment to compensate the nutrition deficiency. As mentioned in my last blog Die for greater good, Autophagy could inhibit the process of apoptosis. Some resistance of chemotherapy can be explained by this mechanism. Cruz-Morcillo MA et al (1) publish a report on Oncogene to discover the mechanism of chemotherapy resistance. 5-FU (5-fluorouracil), combined with other drugs, such like oxaliplatin, could effectively treat colorectal cancer. But in clinic, many patients exhibit resistance of such treatment. The authors found the resistance came from p38MAPK activation. When cancer cells were incubated with 5-FU, they initiate apoptosis signaling cascade, and P38MAPK at the same time. [1] Nat Rev Drug Discov. 2011 Apr;10(4):248. Related Posts: Epidermal Growth Receptor, a target for killing cancer Vandetanib for cancer 1 Vandetanib for cancer 2
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