Abstract
In recent years, multitarget drugs for neurological diseases such as Alzheimer’s disease have been developed and well researched. Many studies have revealed that multitarget drugs are also useful for lung cancer and respiratory diseases. Pemetrexed is a multitargeted antifolate with strong antitumor activity against mesothelioma and lung adenocarcinoma. Crizotinib is an ATP-competitive tyrosine kinase inhibitor that targets c-MET, ROS1, and ALK. Alectinib is known as an ALK inhibitor but also targets LTK, CHEK2, FLT3, PHKG2, and RET. Sorafenib is a tyrosine kinase inhibitor that targets RAF kinase, KIT, VEGFR, PDGFR1β, FLT3, and RET. Nintedanib is a multiple tyrosine kinase inhibitor that targets FGFR, PDGFR, and VEGFR. In this review, we summarize the mechanisms of action of multitarget therapies and report the results of the latest clinical trials.
Highlights
Important discoveries of new drugs have been made based on the strategy of targeting one gene with one drug in one disease [1]
The expanded use of crizotinib for ROS1-positive non-small cell lung cancer (NSCLC) was approved by the US FDA in March 2016 and the European
An application to extend the use of crizotinib to ROS1 fusion gene-positive unresectable advanced recurrent NSCLC was filed in Japan
Summary
Important discoveries of new drugs have been made based on the strategy of targeting one gene with one drug in one disease [1]. This strategy is considered important to prevent the disadvantages of accidental targeting of other substances. Owing to recent discoveries indicating the complexity of intractable diseases such as cancer and neurological diseases, single-target drugs are thought to not be sufficiently effective, and since early 2000, multitarget drugs have been rapidly developed [2]. Because the combination of venlafaxine and fluoxetine to treat depression increases the side effects of anticholinergic activity, a multitarget drug may lead to reduced side effects [3,4,5]. We summarize the mechanisms of action of multitarget therapies and the results of the latest clinical trials and introduce novel compounds and discuss the limitations of multitarget drugs
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