Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology.
Mol Oncol
; 18(3): 479-516, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38158755
ABSTRACT
The initial excitement generated more than two decades ago by the discovery of drugs targeting fatty acid synthase (FASN)-catalyzed de novo lipogenesis for cancer therapy was short-lived. However, the advent of the first clinical-grade FASN inhibitor (TVB-2640; denifanstat), which is currently being studied in various phase II trials, and the exciting advances in understanding the FASN signalome are fueling a renewed interest in FASN-targeted strategies for the treatment and prevention of cancer. Here, we provide a detailed overview of how FASN can drive phenotypic plasticity and cell fate decisions, mitochondrial regulation of cell death, immune escape and organ-specific metastatic potential. We then present a variety of FASN-targeted therapeutic approaches that address the major challenges facing FASN therapy. These include limitations of current FASN inhibitors and the lack of precision tools to maximize the therapeutic potential of FASN inhibitors in the clinic. Rethinking the role of FASN as a signal transducer in cancer pathogenesis may provide molecularly driven strategies to optimize FASN as a long-awaited target for cancer therapeutics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplasms
Limits:
Humans
Language:
En
Journal:
Mol Oncol
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
España