Emerging findings into molecular mechanism of brain metastasis

Cancer Med. 2018 Aug;7(8):3820-3833. doi: 10.1002/cam4.1667. Epub 2018 Jul 10.

Abstract

Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood-brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted "seed and soil" hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis-lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain-specific therapies will be developed for brain metastasis.

Keywords: BRAF; anaplastic lymphoma kinase; blood-brain barrier; brain metastasis; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Blood-Brain Barrier / metabolism
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / secondary*
  • Disease Susceptibility*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Permeability
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Biomarkers