Uncommon targets in non-small cell lung cancer: Everyone wants a slice of cake

Crit Rev Oncol Hematol. 2021 Apr;160:103299. doi: 10.1016/j.critrevonc.2021.103299. Epub 2021 Mar 16.


Target therapies completely changed the clinical approach in EGFR mutated and ALK rearranged non-small cell lung cancer, ensuring these patients exceptional outcomes with a better toxicity profile compared to conventional chemotherapy. In recent years, beyond EGFR and ALK alterations, new data are emerging about less common alterations, new drugs have been already approved and others agents have been recently investigated or are currently under investigation. In this review we will discuss some uncommon alterations in non-small cell lung cancer such as ROS1, BRAF, RET, HER2, NTRK, MET and other targets that are in an early evaluation phase. We will summarize the characteristics of patients harboring these alterations, the already approved or under investigation therapies and the related resistance mechanisms.

Keywords: Non-small cell lung cancer; Resistance mechanism; Target therapy; Uncommon alterations.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins


  • Proto-Oncogene Proteins
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases