What is the mechanism of Sorafenib? from john robert's blog

Sorafenib is a multikinase inhibitor used mainly in the treatment of various cancers, including hepatocellular carcinoma (liver cancer), renal cell carcinoma (kidney cancer) and differentiated thyroid carcinoma. It works by inhibiting several signaling pathways involved in cancer cell proliferation, survival and angiogenesis (the formation of new blood vessels that is needed for tumors to grow) and Sorafenib Price in Malaysia.

Mechanism of Sorafenib:

Sorafenib works by targeting several key kinase pathways that are involved in the growth, survival and spread of cancer cells. These include:

Vascular endothelial growth factor receptor (VEGFR):

Sorafenib inhibits VEGFR-2 and VEGFR-3, which are involved in angiogenesis (the formation of new blood vessels). By blocking VEGFR, sorafenib prevents the formation of blood vessels that provide the tumor with the oxygen and nutrients it needs, effectively starving the tumor and slowing its growth.

Platelet-derived growth factor receptor (PDGFR):

Sorafenib inhibits PDGFR-β, a receptor involved in regulating cell growth, survival, and tumor vessel development. It also disrupts signaling that normally supports tumor growth and spread.

Raf kinases (specifically B-Raf):

Sorafenib inhibits B-Raf and C-Raf kinases, which are part of the Raf/MEK/ERK signaling pathway. This pathway is frequently mutated in cancer (particularly in melanoma) and promotes tumor cell proliferation and survival. Inhibiting Raf kinases prevents abnormal signaling in this pathway, thereby reducing tumor growth and survival.

Fibroblast growth factor receptor (FGFR):

Sorafenib also inhibits FGFR signaling, which is involved in a variety of processes, including cell growth and angiogenesis. By blocking this pathway, sorafenib interferes with the ability of tumor cells to grow and form new blood vessels.

c-Kit:

Sorafenib inhibits c-Kit, a receptor tyrosine kinase that is involved in the growth of many cancers, including gastrointestinal stromal tumors (GIST). By blocking c-Kit signaling, sorafenib may reduce cancer cell proliferation and survival.

Other pathways:

Sorafenib has additional activity against other kinases involved in cancer cell survival and proliferation, including RET (a receptor involved in thyroid cancer) and FLT3 (important in some leukemias).

Summary of Effects:

Angiogenesis Inhibition: By blocking VEGFR and PDGFR, sorafenib reduces the ability of tumors to develop new blood vessels, which limits their growth and ability to metastasize.

Cell Proliferation and Survival Inhibition: By targeting B-Raf and other kinases, sorafenib interferes with cell signaling pathways that promote uncontrolled cell division and survival, helping to slow tumor progression.

Tumor Growth Inhibition: Overall, sorafenib inhibits both the direct growth of cancer cells and the tumor's ability to obtain a blood supply, making it more difficult for tumors to expand.

Clinical Relevance:

Sorafenib has proven effective in the treatment of the following:

Hepatocellular Carcinoma (HCC): It is used to treat advanced or metastatic liver cancer, particularly in patients who are not candidates for surgery or liver transplantation.

Renal cell carcinoma (RCC): It is used in the treatment of advanced kidney cancer.

Differentiated thyroid carcinoma (DTC): In patients with progressive disease who have not responded to iodine therapy.

Administration:

Sorafenib is given orally, usually as tablets.

Treatment is usually continued until the disease progresses or unacceptable side effects occur.

Regular monitoring of liver function, blood pressure and side effects such as skin rash, diarrhoea and hypertension is necessary during treatment. Side effects:

Common side effects of sorafenib include:

Skin rash and hand-foot skin reaction (painful redness and swelling on the palms and soles).

Diarrhea.

Fatigue.

Hypertension (high blood pressure).

Liver toxicity: Increased liver enzymes or liver dysfunction may occur, requiring regular liver monitoring.

Bleeding: The risk of bleeding may be increased.

Conclusion:

The multikinase inhibition mechanism of sorafenib makes it an effective treatment for many types of cancer, particularly those involving solid tumors such as liver, kidney, and thyroid cancer. By targeting key growth and angiogenesis pathways, it helps control tumor progression and limits the tumor's ability to form new blood vessels. However, due to its broad kinase activity, sorafenib can cause significant side effects, which require careful monitoring throughout treatment.