In recent years, molecular targeted therapy has emerged as a new cancer treatment method. Compared with traditional therapy, molecular targeted therapy has improved targeting, can specifically kill tumor cells and reduce damage to normal tissues, has low rates of drug resistance, and is safer and better tolerated by patients. In 1906, Enrlich first proposed the concept of targeted drug delivery, that is, to use a specific carrier to selectively deliver drugs or other antitumor active substances to the target site, therefore limiting the therapeutic effect or drug effect to specific target cells, tissues, or organs as far as possible, without affecting the function of their normal counterparts, so as to improve efficacy and reduce adverse reactions.

Molecular targeted therapy targets overexpressed cell receptors, key genes, and some marker molecules of tumor cells by selecting specific blockers to inhibit tumor growth, progress, and metastasis. The principle of molecular targeted therapy is to target key genes and signaling pathways in the process of tumor development, or the proto oncogene, tumor suppressor gene, and suicide gene, among others, by designing small molecule inhibitors to reverse the biological behavior of tumor cells at the molecular level, so as to inhibit the proliferation and metastasis of tumor cells. At present, there are dozens of molecular targeted drugs both on the market and in the clinical research stage, including sorafenib, regorafenib, lenvatinib, cabozantinib, and other drugs, which have achieved significant results

Sorafenib

Sorafenib is a broad-spectrum, small molecule inhibitor that can inhibit the expansion, angiogenesis, and apoptosis of many tumor cells.12 Sorafenib primarily targets serine/threonine kinase, vascular endothelial growth factor receptor (VEGFR), Platelet-derived growth factor receptor beta (PGFRβ), Kit, fms-like tyrosine kinase-3 (FLT3), ret proto-oncogene (RET), and other receptor tyrosine kinases to inhibit tumor cell proliferation and angiogenesis, which subsequently inhibits tumor growth.  In 602 patients with advanced HCC who had not received systematic treatment before, the median survival time of the sorafenib group was 2.8 months longer than that of placebo group (44%). There was a significant difference between the sorafenib group and the placebo group.The patients with advanced HCC had good tolerance to sorafenib, indicating that sorafenib can be used as a first-line drug to treat patients with advanced HCC.

Regorafenib

The molecular structures of regorafenib and sorafenib are very similar, as are their mechanisms of action.8 However, regorafenib has higher biological activity than sorafenib, capable of widely inhibiting the kinases related to angiogenesis and tumorigenesis, such as VEGFR 1-3, tyrosine protein kinase receptor Tie, RET, PDFGR, basic fibroblast growth factor receptor (FGFR), serine/threonine protein kinase RAF, mitogen-activated protein, and kinase p38, so as to play an antitumor role.

The researchers tested regorafenib as a second-line drug in 573 patients with HCC who had been treated with sorafenib, 194 of whom received placebo.The final data showed that, compared with the placebo group, regorafenib significantly improved the overall patient survival time from 7-8 months in the placebo group to 10.6 months in the experimental group. In 2 of the patients treated with regorafenib, the tumor shrank to an undetectable state.These data indicate that regorafenib has a good therapeutic effect in patients with HCC who have been treated with sorafenib.

Lenvatinib

Lenvatinib is an inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, and tyrosine protein kinase receptor RET and Kit.In June 2017, the annual meeting of the American Society of Clinical Oncology reported the phase III clinical research results of lenvatinib in the first-line treatment of unresectable liver cancer. It was found that the total survival time of the main clinical end point in the lenvatinib group was longer than that of the sorafenib group (13.6 vs 12.3 months), and the secondary clinical end point in the lenvatinib group was also significantly better than that of the sorafenib group, including progression-free survival time (7.4 vs 3.7 months), disease progression time (8.9 vs 3.7 months), and objective remission rate (24% vs 9%). Although the main clinical end point overall survival of the lenvatinib group and sorafenib group did not reach statistical difference, progression-free survival of the lenvatinib group was twice as long as that of the sorafenib group, and time to progress was nearly 3 times longer than that of sorafenib group.

Jessica

Managing Editor

Pancreatic disorder and therapy