ROS1 as a 'druggable' receptor tyrosine kinase

Lessons learned from inhibiting the ALK pathway

Sai Hong Ignatius Ou, Jackie Tan, Yun Yen, Ross A. Soo

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

ROS1 is one of 58 receptor tyrosine kinases, and one of two orphan receptor tyrosine kinases where its ligand is unknown. ROS1 is evolutionarily related to ALK. ROS1 rearrangement was discovered in glioblastoma in 1987, in non-small-cell lung cancer (NSCLC) in 2007, and in cholangiocarcinoma in 2011. While the clinicopathologic characteristics of ROS1-rearranged glioblastoma and cholangiocarcinoma patients remain to be defined, the clinicopathologic characteristics of ROS1-rearranged NSCLC patients have recently been described. Although ROS1 shares only 49% amino acid sequence homology with ALK in the kinase domains, several ALK inhibitors have demonstrated in vitro inhibitory activity against ROS1. With the recent US approval of crizotinib, a multi-targeted ALK/MET kinase inhibitor, for the treatment of ALK-rearranged NSCLC, attention has turned to ROS1-rearranged tumors, especially NSCLC. The next few years should witness a rapid pace of clinical research in ROS1-rearranged tumors utilizing available ALK inhibitors.

Original languageEnglish
Pages (from-to)447-456
Number of pages10
JournalExpert Review of Anticancer Therapy
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

Receptor Protein-Tyrosine Kinases
Non-Small Cell Lung Carcinoma
Cholangiocarcinoma
Glioblastoma
Phosphotransferases
Amino Acid Sequence Homology
Neoplasms
Ligands
Research
Therapeutics

Keywords

  • ALK inhibitor
  • CD74-ROS1
  • cholangiocarcinoma
  • crizotinib
  • driver mutation
  • FIG-ROS1
  • glioblastoma multiforme
  • non-small-cell lung cancer
  • personalized medicine
  • ROS1 inhibitor
  • ROS1 receptor tyrosine kinase
  • SLC34A2-ROS1

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Oncology

Cite this

ROS1 as a 'druggable' receptor tyrosine kinase : Lessons learned from inhibiting the ALK pathway. / Ou, Sai Hong Ignatius; Tan, Jackie; Yen, Yun; Soo, Ross A.

In: Expert Review of Anticancer Therapy, Vol. 12, No. 4, 04.2012, p. 447-456.

Research output: Contribution to journalArticle

Ou, Sai Hong Ignatius ; Tan, Jackie ; Yen, Yun ; Soo, Ross A. / ROS1 as a 'druggable' receptor tyrosine kinase : Lessons learned from inhibiting the ALK pathway. In: Expert Review of Anticancer Therapy. 2012 ; Vol. 12, No. 4. pp. 447-456.
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