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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.
Up to 7% of NSCLC patients have EML4-ALK translocations or mutations in the ROS1 gene; these patients may benefit from ALK inhibitors, which are now approved for this subset of patients. [57] Crizotinib, which gained FDA approval in August 2011, is an inhibitor of several kinases, specifically ALK, ROS1, and MET.
It restricts and constrains learning and long-term memory [27] [55] [44] and small-molecule inhibitors of the ALK receptor can improve learning, [27] long-term memory, [55] and extend healthy lifespan. [56] ALK is also a candidate thinness gene, as its genetic deletion leads to resistance to diet- and leptin-mutation-induced obesity. [57] [N 1]
Also, patients who tested negative for EML4/ALK fusion had a response rate to crizotinib of up to 35%. [20] According to patient advocacy group ALK Positive, a study in December 2018 found that the median survival for people with stage 4 (IV) ALK-positive lung cancer was 6.8 years with the right care. [4]
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]
Alectinib (INN [8]), sold under the brand name Alecensa, is an anticancer medication that is used to treat non-small-cell lung cancer (NSCLC). [6] [7] It blocks the activity of anaplastic lymphoma kinase (ALK). [9] [10] It is taken by mouth. [6] It was developed by Chugai Pharmaceutical Co. Japan, which is part of the Hoffmann-La Roche group.
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.
Approval required a companion molecular test for the EML4-ALK fusion. In March 2016, the FDA approved crizotinib in ROS1-positive non-small cell lung cancer. [19] In October 2012, the European Medicines Agency (EMA) approved the use of crizotinib to treat non-small cell lung cancers that express the abnormal anaplastic lymphoma kinase (ALK ...