A Review of the World’s Lung Cancer Targeting Drugs

The lung cancer incidence increasingly rises and draws much attention under the environment that the haze becomes increasingly serious and the air for the survival of human kinds becomes worse and worse. In China, lung cancer is the cancer with the highest incidence among all the cancers, accounting for more than 10% of all cancers. It is already the middle and advanced stage when patients with lung cancer are diagnosed because its early symptoms are not apparent. As a result, the basis for many lung cancer patients to "sustain their lives" is the necessary effective targeting drug treatment. I will review the world’s lung cancer targeting drugs in the followings.

Table 1 World’s lung cancer targeting drugs

       Seen from Table 1, Roche has Eriotinib, Alectinib and Bevacizumab among the multiple lung cancer targeting drug manufacturers, and is the pharmaceutical enterprise with the most lung cancer targeting drugs, with many targets involved including EGFR, ALK and VEGF, wherein, as a lung cancer drug newly approved to be marketed in 2016, Alectinib is used to treat metastatic/advanced ALK-positive non-small cell lung cancer (NSCLC) and mainly for patients whose disease has progressed on or who are intolerant of Crizotinib, a lung cancer drug under Pfizer. As a kinase inhibitor targeting ALK, Alectinib can inhibit ALK phosphorylation and ALK-mediated downstream targets STAT3 and AKT, and furthermore, the major metabolite M4 of Alectinib has been proved to have good activity and potency in vitro and in vivo experiments.

       In addition, AstraZeneca also has two lung cancer drugs: Gefitinib and Osimertinib. Unlike Roche, AstraZeneca has been focusing on the study of EGFR lung cancer drugs, therefore, both Gefitinib and Osimertinib are lung cancer targeting drug for such target. Both those two new NSCLC drugs were approved by FDA in 2015 as epidermal growth factor receptor (EGFR) inhibitor, and can block the signaling pathway that leads to tumor growth and spread. Studies show that EGFR has high expression in multiple cancer cells, especially in NSCLC cells.

       By contrast, Eli Lilly, which also possesses two lung cancer drugs, is far behind AstraZeneca in lung cancer drug market share. Gefitinib under AstraZeneca has been used as a front-line regimen for lung cancer and can be used alone, but Eli Lilly’s Necitumumab is only approved to be used for treating lung cancer in combination with gemcitabine and cisplatin, and only for the squamous NSCLC that accounts for about one-third of all lung cancers; another lung cancer drug Ramucirumab under Eli Lilly belongs to monoclonal antibody and is an injection, therefore, it has no advantage in price and use risk and has not occupied a large market share.

       There has been the enthusiasm for the R&D of PD-1/PD-L1 recently in China and foreign countries, which is also a hot target in lung cancer treatment. Currently, the PD-1 inhibitors approved to go to market by FDA only include Merck & Co.’s pembrolizumab (trade name: Keytruda) and BMS’ Nivolumab (trade name: Opdivo), both of which obtained FDA’s breakthrough designation and have been used for lung cancer treatment. FDA approved Nivolumab, the first PD-1 inhibitor approved in the world, to be used for advanced squamous NSCLC in 2015; as a monoclonal antibody, Nivolumab can bind to PD-1 inhibitor and inhibits its interaction with PD-L1 and PD-L2, thereby lifting PD-1’s inhibition of cancer immune response and achieving the lung cancer therapeutic effect. FDA accelerated approval of Merck & Co.’s Pembrolizumab in September 2016, making it another front-line regimen for lung cancer.

       The development of lung cancer drugs will become increasingly more, as the lung cancer incidence constantly rises. And with the enthusiasm for the R&D of PD-1 and other new targets, predictably, the lung cancer drugs specific to PD-1 will also come one after another. Let’s work together to fight against the lung cancers.