Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers.

Journal Article (Journal Article;Review)

The management of non-small cell lung cancer (NSCLC) has transformed with the discovery of therapeutically tractable oncogenic drivers. In addition to activating driver mutations, gene fusions or rearrangements form a unique sub-class, with anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) targeted agents approved as the standard of care in the first-line setting for advanced disease. There are a number of emerging fusion drivers, however, including neurotrophin kinase (NTRK), rearrangement during transfection (RET), and neuregulin 1 (NRG1) for which there are evolving high-impact systemic treatment options. Brain metastases are highly prevalent in NSCLC patients, with molecularly selected populations such as epidermal growth factor receptor (EGFR) mutant and ALK-rearranged tumors particularly brain tropic. Accordingly, there exists a substantial body of research pertaining to the understanding of brain metastases in such populations. Little is known, however, on the molecular mechanisms of brain metastases in those with other targetable fusion drivers in NSCLC. This review encompasses key areas including the biological underpinnings of brain metastases in fusion-driven lung cancers, the intracranial efficacy of novel systemic therapies, and future directions required to optimize the control and prevention of brain metastases.

Full Text

Duke Authors

Cited Authors

  • Tan, AC; Itchins, M; Khasraw, M

Published Date

  • February 19, 2020

Published In

Volume / Issue

  • 21 / 4

PubMed ID

  • 32093103

Pubmed Central ID

  • PMC7073114

Electronic International Standard Serial Number (EISSN)

  • 1422-0067

Digital Object Identifier (DOI)

  • 10.3390/ijms21041416


  • eng

Conference Location

  • Switzerland