ROS1: A Driver of NSCLC Oncogenesis1,2

ROS1 genetic rearrangements, both inter- and intra-chromosomal, lead to constitutive activation of the ROS1 kinase1-4

  • Genetic rearrangements in the tyrosine kinase receptor ROS1 lead to the development of fusion proteins1
ROS1 gene fusion and fusion protein ROS1 gene fusion and fusion protein
  • ROS1 fusion proteins are constitutively active and drive downstream signaling pathways such as AKT or MEK, depending on the ROS1 fusion partner1
  • Constitutive activation of these signaling pathways can result in cell proliferation and tumorigenesis1,2

ROS1 rearrangements and pathway activation1,5-7

ROS1 rearrangements and pathway activation ROS1 rearrangements and pathway activation

 

AKT=v-akt murine thymoma viral oncogene homologue; ERK=extracellular signal-regulated kinase; JAK=Janus kinase; MEK=mitogen-activated protein kinase; mTOR=mammalian target of rapamycin; NSCLC=non-small cell lung cancer; PI3K=phosphatidylinositol-4,5-bisphosphate 3-kinase; RAF=rapidly accelerated fibrosarcoma kinase; Ras=rat sarcoma kinase; ROS1=ROS proto-oncogene 1; STAT=signal transducer and activator of transcription.

ROS1 fusion proteins are the primary oncogenic drivers in some patients with NSCLC1

  • ROS1 rearrangements primarily occur in the absence of other known oncogenic drivers in NSCLC1
  • The prevalence of ROS1 rearrangement in NSCLC is 1-2%. The majority of these cases exhibit adenocarcinoma histology1,8
  • Approximately 20,000 patients worldwide are diagnosed with ROS1+ NSCLC per year1,9

References

  1. Davies KD, Doebele RC. Clin Cancer Res. 2013;19(15):4040-4045. PMID: 23719267
  2. Chong CR, Bahcall M, Capelletti M. Clin Cancer Res. 2017;23(1):204-213. PMID: 27370605
  3. Cancer Genome Atlas Research Network. Nature. 2014;511(7511):543-550. PMID: 25079552
  4. Rossi G, Jocollé G, Conti A, et al. Lung Cancer (Auckl). 2017;8:45-55. PMID: 28740441
  5. Davies KD, Le AT, Theodoro MF. Clin Cancer Res. 2012;18(17):4570-4579. PMID: 22919003
  6. Morgan GJ, He J, Tytarenko R, et al. Leukemia. 2018. PMID: 29654269
  7. Zhu Y, Lin X, Li X, et al. Thorac Cancer. 2018;9(1):159-163. PMID: 28971587
  8. Bergethon K, Shaw AT, Ou SH, et al. J Clin Oncol. 2012;30(8):863-870. PMID: 22215748
  9. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. CA Cancer J Clin. 2018;0(0):1-31. PMID: 30207593