The rationale for druggability of CCDC6-tyrosine kinase fusions in lung cancer

Mol Cancer. 2018 Feb 19;17(1):46. doi: 10.1186/s12943-018-0799-8.

Abstract

Gene fusions occur in up to 17% of solid tumours. Oncogenic kinases are often involved in such fusions. In lung cancer, almost 30% of patients carrying an activated oncogene show the fusion of a tyrosine kinase to an heterologous gene. Several genes are partner in the fusion with the three kinases ALK, ROS1 and RET in lung. The impaired function of the partner gene, in combination with the activation of the kinase, may alter the cell signaling and promote the cancer cell addiction to the oncogene. Moreover, the gene that is partner in the fusion to the kinase may affect the response to therapeutics and/or promote resistance in the cancer cells. Few genes are recurrent partners in tyrosine kinase fusions in lung cancer, including CCDC6, a recurrent partner in ROS1 and RET fusions, that can be selected as possible target for new strategies of combined therapy including TKi.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Lung / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins c-ret / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • CCDC6 protein, human
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases