Related Experiment Video

Updated: May 23, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

ROS1 as a 'druggable' receptor tyrosine kinase: lessons learned from inhibiting the ALK pathway

Sai-Hong Ignatius Ou1, Jackie Tan, Yun Yen

  • 1Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA 92868, USA. ignatius.ou@uci.edu

Expert Review of Anticancer Therapy
|April 17, 2012
PubMed

Insights

ROS1 rearrangements are found in various cancers, including non-small-cell lung cancer (NSCLC). Existing ALK inhibitors show promise for treating ROS1-rearranged tumors, particularly NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ROS1 is an orphan receptor tyrosine kinase, evolutionarily related to ALK.
  • ROS1 rearrangements have been identified in glioblastoma, non-small-cell lung cancer (NSCLC), and cholangiocarcinoma.
  • Clinicopathologic features of ROS1-rearranged NSCLC are increasingly understood, while those in other cancers require further definition.

Purpose of the Study:

  • To review the current understanding of ROS1 rearrangements in cancer.
  • To explore the potential of ALK inhibitors for treating ROS1-rearranged malignancies.
  • To highlight the emerging clinical research landscape for ROS1-driven cancers.

Main Methods:

  • Literature review of ROS1 rearrangements and their clinical implications.
  • Analysis of existing data on ALK inhibitors' efficacy against ROS1.
  • Synthesis of information on clinicopathologic characteristics of ROS1-rearranged cancers.

Main Results:

  • ROS1 rearrangements occur in glioblastoma, NSCLC, and cholangiocarcinoma.
  • Despite limited homology, ALK inhibitors demonstrate in vitro activity against ROS1.
  • Crizotinib, an approved ALK/MET inhibitor, offers a potential therapeutic avenue for ROS1-rearranged NSCLC.

Conclusions:

  • ROS1-rearranged NSCLC is a distinct clinicopathologic entity.
  • Available ALK inhibitors represent a promising therapeutic strategy for ROS1-driven tumors.
  • Accelerated clinical research is anticipated for ROS1-rearranged cancers using existing ALK inhibitors.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...