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Thursday, March 1, 2018

ALK inhibitor

Perfect ALKemy: Optimizing the Use of ALK-Directed Therapies in ...
src: clincancerres.aacrjournals.org

ALK inhibitors are potential anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation.


Video ALK inhibitor



EML4-ALK

About 4-7% of non-small cell lung carcinomas (NSCLC) have EML4-ALK translocations.

Approved inhibitors

  • crizotinib (Xalkori) (also a ROS1 inhibitor) approved in Aug 2011 by the US FDA for ALK-positive NSCLC.
  • ceritinib (Zykadia), approved by the FDA in April 2014 for treatment of NSCLC.
  • alectinib (Alecensa) (Chugai, NDA has been filed in Japan) (breakthrough status in U.S.) FDA approved Dec 2015 (accelerated), full approval in 2017 for ALK-positive NSCLC.

Maps ALK inhibitor



Clinical trials

Additional ALK inhibitors currently (or soon to be) undergoing clinical trials include:

  • Dalantercept, ACE-041 (Acceleron)
  • Brigatinib (AP26113) (by Ariad) (breakthrough status in U.S.) (also an EGFR inhibitor)
  • Entrectinib (Nerviano's NMS-E628, licensed by Ignyta and renamed RXDX-101, in the U.S. orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA-, TrkB-, TrkC-, ROS1- and ALK-positive NSCLC)
  • PF-06463922 (Pfizer)
  • TSR-011 (Tesaro)
  • CEP-37440 (Teva)
  • X-396 (Xcovery)

Updates for several of these will be available at the start of June at ASCO 2014.

Discontinued

  • ASP-3026 (Astellas)

Molecular Mechanisms of Resistance to First- and Second-Generation ...
src: cancerdiscovery.aacrjournals.org


NPM-ALK

NPM-ALK is a different variation/fusion of ALK that drives anaplastic large-cell lymphomas (ALCLs) and is the target of other ALK inhibitors.


Molecular Mechanisms of Resistance to First- and Second-Generation ...
src: cancerdiscovery.aacrjournals.org


References


ALK Mutations Conferring Differential Resistance to Structurally ...
src: clincancerres.aacrjournals.org


External links

  • alkinhibitors.com
  • ALK inhibitor discussion forum

Source of the article : Wikipedia