ROS1 Inhibitor


ROS1 Inhibitor, ROS1 Gene Encoded Tyrosine Kinase Receptor Antagonist

  • Indications
  1. Lung Adenocarcinoma (ROS1+, metastatic)
  • Mechanism
  1. ROS1 Tyrosine-Protein Kinase
    1. Proto-oncogene ROS is encoded by the ROS1 gene
    2. ROS is a Protein associated with cell growth, via Tyrosine phosphorylation and receptor-mediated signaling
    3. Member of the sevenless subfamily of Tyrosine KinaseInsulin receptor genes
  2. ROS1 Inhibitors are small molecule, Tyrosine Kinase Inhibitors specific to ROS1 receptors
    1. Agents that block ROS1, suppress specific tumor cell growth
  • Medications
  1. Crizotinib (Xalkori)
    1. Also targets ALK (See ALK Inhibitor)
    2. Also blocks c-Met/hepatocyte growth factor receptor (HGFR)
    3. Adverse Effects include ILD, hepatotoxicity, Bradycardia, QT Prolongation
  2. Entrectinib (Rozlytrek)
    1. Also targets NTRK (See NTRK Inhibitor)
    2. Risk of Neurotoxicity, Hepatotoxicity, skeletal Fractures, cardiotoxicity, Prolonged QTc, Hyperuricemia, ocular toxicity
    3. Avoid with strong CYP3A4 Inhibitors and inducers
  • Dosing
  1. See other references for disease specific dosing protocols
  • Safety
  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, pregnancy category X)
    1. Use reliable Contraception
  • Adverse Effects (based on Entrectinib)
  1. Cardiotoxicity
  2. Cognitive Impairment
  3. Fractures
  4. Hepatotoxicity
  5. Ocular Toxicity