Fatty acid synthase: a druggable driver of breast cancer brain metastasis.
Expert Opin Ther Targets
; 26(5): 427-444, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35545806
ABSTRACT
INTRODUCTION:
Brain metastasis (BrM) is a key contributor to morbidity and mortality in breast cancer patients, especially among high-risk epidermal growth factor receptor 2-positive (HER2+) and triple-negative/basal-like molecular subtypes. Optimal management of BrM is focused on characterizing a 'BrM dependency map' to prioritize targetable therapeutic vulnerabilities. AREAS COVERED We review recent studies addressing the targeting of BrM in the lipid-deprived brain environment, which selects for brain-tropic breast cancer cells capable of cell-autonomously generating fatty acids by upregulating de novo lipogenesis via fatty acid synthase (FASN). Disruption of FASN activity impairs breast cancer growth in the brain, but not extracranially, and mapping of the molecular causes of organ-specific patterns of metastasis has uncovered an enrichment of lipid metabolism signatures in brain metastasizing cells. Targeting SREBP1-the master regulator of lipogenic gene transcription-curtails the ability of breast cancer cells to survive in the brain microenvironment. EXPERT OPINION Targeting FASN represents a new therapeutic opportunity for patients with breast cancer and BrM. Delivery of brain-permeable FASN inhibitors and identifying strategies to target metabolic plasticity that might compensate for impaired brain FASN activity are two potential roadblocks that may hinder FASN-centered strategies against BrM.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Neoplasias da Mama
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Expert Opin Ther Targets
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Espanha