CNS Metastasis in ROS1+ NSCLC

ROS1+ NSCLC demonstrates metastatic potential in the CNS1

  • Approximately 20% of patients with ROS1+ NSCLC have metastases located in the brain at initial presentation1,2
  • CNS metastasis is associated with significant morbidity and poor survival3
    • Substantial neurological impairment is common
    • Median survival of untreated patients is 4 to 7 weeks

The blood-brain barrier creates a sanctuary for metastatic disease4

  • Not all molecules can cross the blood-brain barrier. In order to cross, molecules need to be small and lipophilic4
  • Of those that do cross, depending on their chemical structure, some small molecules are removed from the CNS after they pass through the blood-brain barrier through efflux activity4
  • The blood-brain barrier is reinforced by P-gp, a drug-efflux-transporter protein, which actively removes a broad range of P-gp substrates from the endothelial cell cytoplasm before they cross into the CNS4

Transport routes in the blood-brain barrier5

Blood-brain barrier routes Blood-brain barrier routes

 

[Reprinted from NeuroRx, Vol 2/edition 1, Löscher W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family, 86-98, Copyright 2005, with permission from Elsevier.]

BCRP=breast cancer resistance protein; CNS=central nervous system; MRP=multidrug resistance protein; NSCLC=non–small cell lung cancer; Pgp=P-glycoprotein; ROS1=ROS proto-oncogene 1.

References

  1. Gainor JF, Tseng D, Yoda S, et al. JCO Precis Oncol. 2017. PMID: 29333528
  2. Park S, Ahn BC, Lim SW, et al. J Thorac Oncol. 2018;13(9):1373-1382. PMID: 29883837
  3. Chi A, Komaki R. Cancers (Basel). 2010;2(4):2100-2137. PMID: 24281220
  4. Deeken JF, Löscher W. Clin Cancer Res. 2007;13(6):1663-1674. PMID: 17363519
  5. Löscher W, Potschka H. NeuroRx. 2005;2(1):86-98. PMID: 15717060