Researchers have discovered that entrectinib, a new multitarget inhibitor for cancer therapy, is well tolerated with an acceptable safety profile, as published in Biomedicine & Pharmacotherapy.

Over the last century, clinical researchers have largely stuck to the unspoken dogma of “one therapeutic drug, one target, one disease,” the authors said. Although this approach has yielded clinical success, scientists are discovering that diseases are often related to various receptors and signaling pathways. With diseases that are multifaceted in nature, the targeting of 1 factor alone is unlikely to yield satisfactory results.

Hence, the paradigm has slowly shifted towards multitarget therapeutics, which is the targeting of multiple targets that are associated with a particular disease. As a result of this change in thinking, many new drugs for various diseases have been developed.

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One such drug is entrectinib. “Entrectinib, also known as RxDX-101 or NMS-E628, inhibits the rearrangement of TRKA, TRKB, TRKC, ALK and ROS1, and has shown efficacy in tumors with NTRK1/3, ALK and ROS1 changes,” the authors of the study wrote. In Japan, entrectinib has been approved for a number of diseases, including medullary thyroid carcinoma (MTC), thyroid cancer, pancreatic cancer, and more.

In simpler terms, entrectinib is a multitarget antitumor inhibitor that can cross the blood-brain barrier. Importantly, current research indicates that this drug is well-tolerated and has an acceptable safety profile. This drug has been tested on patients with colorectal cancer, nonsmall cell lung cancer, and brain metastases.

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The potential of drugs such as entrectinib is that it targets biomarkers as opposed to tumor locations; hence, it can be considered a form of “precision therapy.” This allows physicians to use molecular markers and advanced diagnostic technology to select the most suitable drugs to be prescribed to certain patients. The emergence of entrectinib should encourage further research to develop second- and third-generation inhibitors based on their structure. 


Jiang Q, Li M, Li H, Chen L. Entrectinib, a new multi-target inhibitor for cancer therapyBiomed Pharmacother. Published online April 18, 2022. doi:10.1016/j.biopha.2022.112974