Receptor tyrosine kinases activate two primary pathways which are PI3K pathway which moves down through AKT and MAPK pathway which passes down through ERK1/2. Many cancers are associated with the hyperactivation of the MAPK pathway. This pathway starts from Ras and moves through Raf, MEK1/2 and ERK1/2 (the final effector molecule). Scientists have used sophisticated techniques like high throughput screening methods to discover novel molecules like Sorafenib, which can target this MAPK pathway.

Osteosarcoma is bone tumor which shows a high rate of metastasis. Normal chemotherapeutic agents have failed to attain a complete success over this problem due to the resistance offered by these cell lines and overexpression of P-glycoprotein. The chemical libraries were screened, to discover an agent which can project a different mechanism of treatment like targeting RTKs. The metastasis of rhabdomyosarcoma and Osteosarcoma involve RTKs, like KIT, VEGFR-2, VEGFR-3 and PDGFR-β. Another protein which plays a vital role in metastasis is ezrin which is a linker protein present in cytoskeleton. Ezrin belongs to ERM family. Matrix metalloproteinase – 2 and 9 are involved in the process of tumerogenesis. Initially Sorafenib was considered to target Raf kinases (BRAF, RAF-1, BRAF ^V600E) and hence block the MAPK pathway. Later on it was discovered to be a multi-kinase inhibitor which could inhibit the action of RTKs involved in tumor progression and angiogenesis. It deactivates the anti-apoptotic proteins like MCL-1 and hence induces the cell death within cells through the process of apoptosis. Sorafenib has a Biarylureic structure and has proved its efficacy in case of cancers related to liver, kidney and thyroid gland. Preclinical studies have shown that Sorafenib can inhibit MCL-1, ERM and ERK1/2 pathways within osteosarcoma cell lines under both in vitro and in vivo conditions. Hence it acts as an angiogenesis inhibitor and inhibits the spread of cancer to lungs [1].

Phase II clinical trials have been done to asses the action of Sorafenib in case of advanced metastatic melanoma. When it was administered alone it showed limited action. It did not show any prominent effect on Ki67 or cyclin D1 and there was no direct correlation between the BRAF^V600E mutation and the clinical activity of this inhibitor. These results suggest that it does not specifically target BRAF [2].

A common side effect of this inhibitor under physiological conditions is the synthesis of secondary erythrocytes at an increased rate. This condition is also known as erythropoiesis and leads to the slow progress of anemia [3]. Sorafenib has been found to be effective in case of hepatocellular carcinoma (advanced stages) both alone and in combination with other inhibitors like doxorubicin. It inhibited the growth of tumor in a dose dependent manner. This agent gets metabolized in liver through cyt P4503A4 and UDG-transferase1A9 [4].

Sorafenib is a single multi-kinase inhibitor which controls the growth of tumor, angiogenesis and metastasis of cancer. It is a single agent showing multifarious effects.