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ALK Biological Pathways Reviews
ALK
Anaplastic lymphoma kinase; ALK tyrosine kinase receptor; CD246; CD246 antigen; NBLST3
ALK is a tyrosine kinase receptor that resides on chromosome 2p23. Chromosomal rearrangements resulting in fusion genes leads to ALK tyrosine kinase that promote cell survival by activating a signaling pathway or by inhibition of apoptosis, which leads to cell proliferation.1
Understanding the Role of ALK
This animation explains the role of the ALK oncogene in normal cellular functioning and the effect of an abnormal translocation event where ALK fuses to another gene.
Expression in Cancer
ALK-positivity is found in a variety of cancer types. The graphic below displays the expression of ALK-positivity in up to a certain percentage of cases in each cancer type.
ALK Targeting Anticancer Drugs
ALK inhibitors are anticancer drugs that target and treat tumors with variations of ALK. ALK inhibitors are a type of tyrosine kinase inhibitor, which inhibit proteins involved in the abnormal growth of cancer cells. This table outlines therapies targeting ALK both approved by the FDA and in the pipeline.
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ALK Targeting Anticancer Drugs Approved by the FDAa |
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Brand Name (Generic Drug Name) |
Indications |
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Alecensa (alectinib)1 |
Treatment of patients with ALK-positive metastatic NSCLC, as detected by an FDA-approved test |
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Alunbrig (brigatinib)2 |
First-line treatment of patients with ALK-positive metastatic NSCLC, as detected by an FDA-approved test |
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Lorbrena (lorlatinib)3 |
Treatment of patients with ALK-positive metastatic NSCLC, as detected by an FDA-approved test |
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Xalkori (crizotinib)4 |
Treatment of patients with metastatic NSCLC whose tumors are ALK- or ROS1-positive, as detected by an FDA-approved test |
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Treatment of pediatric patients aged ≥1 years and young adults with ALK-positive, relapsed or refractory, systemic anaplastic large-cell lymphoma |
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Zykadia (ceritinib)5 |
Treatment of patients with ALK-positive metastatic NSCLC, as detected by an FDA-approved test |
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ALK Targeting Anticancer Drugs in the Pipelineb |
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Generic Drug Name |
Potential Indications |
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APG 24496 |
Being evaluated for the treatment of patients with ALK-positive NSCLC and other solid tumors |
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NVL 6557 |
Being evaluated for the treatment of patients with advanced, ALK-positive NSCLC and other solid tumors |
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SAF-189 (foritinib)8 |
Being evaluated for the treatment of patients with ALK- or ROS1-positive NSCLC |
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TPX-0005 (repotrectinib)9 |
Being evaluated for the treatment of patients with TKI-naïve and TKI-pretreated patients with ALK- or ROS1-positive NSCLC and advanced, NTRK-positive solid tumors |
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TPX-013110 |
Being evaluated for the treatment of patients with ALK-positive, advanced NSCLC |
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TQ-B313911 |
Has shown promise in the treatment of patients with ALK- or ROS1-positive, advanced NSCLC |
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WX-0593 (Iruplinalkib)12 |
Has shown promise in the treatment of patients with ALK- or ROS1-positive, advanced NSCLC |
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X-396 (ensartinib)13 |
Being evaluated for the treatment of patients with ALK-positive, advanced solid tumors |
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Being evaluated for the treatment of patients with ALK-positive NSCLC |
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ZG-0418 (alkotinib)14 |
Being evaluated for the treatment of patients with ALK-positive NSCLC |
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ZL-230215 |
Being evaluated for the treatment of patients with ALK-positive NSCLC who developed crizotinib resistance and/or brain metastasis |
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ALK, epidermal growth factor receptor; BTK, Bruton's tyrosine kinase; cGVHD, chronic graft versus host disease; CLL, chronic lymphocytic leukemia; CNSL, central nervous system lymphoma; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; GCB, germinal center B-cell like; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; NSCLC, non-small-cell lung cancer; R/R, relapsed and/or refreactory; SLL, small lymphocytic lymphoma; WM, Waldenström’s macroglobulinemia.
aAdapted from prescribing information.1-5 b Adapted from manufacturer websites.6-15 |
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