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ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation. [1] They fall under the category of tyrosine kinase inhibitors , which work by inhibiting proteins involved in the abnormal growth of tumour cells.
Brigatinib is an inhibitor of ALK [3] and mutated EGFR. [5]ALK was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL.
ALK positive lung cancer is a primary malignant lung tumor whose cells contain a characteristic abnormal configuration of DNA wherein, most frequently, the echinoderm microtubule-associated protein-like 4 gene is fused to the anaplastic lymphoma kinase (ALK) gene.
Ensartinib, sold under the brand name Ensacove, is an anti-cancer medication used for the treatment of non-small cell lung cancer. [1] Ensartinib is an Anaplastic lymphoma kinase (ALK) inhibitor used as the salt ensartinib hydrochloride. [1] It is taken by mouth. [1]
Entrectinib, sold under the brand name Rozlytrek, is an anti-cancer medication used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. [5] It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin receptor kinases (TRK) A, B and C, C-ros oncogene 1 ( ROS1 ) and anaplastic lymphoma kinase (ALK).
ALK, i.e. anaplastic lymphoma kinase, is a protein product of the ALK gene located on chromosome 2. In ALK-positive ALCL, a portion of the ALK gene has merged with another site on the same or different chromosome to form a chimeric gene consisting of part of the new site and part of the ALK gene coding for ALK's activity. [4]
Ceritinib is an anaplastic lymphoma kinase (ALK) inhibitor primarily used for the treatment of ALK positive metastatic NSCLC. [8] [9] Previously, it was only indicated for patients who had developed resistant to crizotinib, another ALK inhibitor, but has since had its usage expanded to serve as a primary option for metastatic NSCLC.
Up to 7% of those with NSCLC harbor mutations that result in hyperactive ALK protein, which can be treated with ALK inhibitors crizotinib, or its successors alectinib, brigatinib, and ceritinib. [45] Those treated with ALK inhibitors who relapse can then be treated with the third-generation ALK inhibitor lorlatinib. [45]
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