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Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology.

Author information

Affiliations

  • 1. Metabolism & Cancer Group, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Girona, Spain.
      Authors
    • Menendez JA 1
    • Cuyàs E 1
    • Verdura S 1
    • Llop-Hernández À 1
    • López J 1
    • Serrano-Hervás E 1, 4
    • Martin-Castillo B 1
    (7 authors)
  • 2. Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cell Biology Institute (IBMC), Miguel Hernández University (UMH), Elche, Spain.
      Authors
    • Encinar JA 2
    (1 author)
  • 3. Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
      Authors
    • Vander Steen T 3
    • Lupu R 3
    (2 authors)
  • 4. CompBioLab Group, Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química, Universitat de Girona, Girona, Spain.
      Authors
    • Serrano-Hervás E 1, 4
    • Osuna S 4
    (2 authors)

ORCIDs linked to this article

Molecular Oncology, 18 Jan 2024, 18(3):479-516
https://doi.org/10.1002/1878-0261.13582 PMID: 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.

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Read article at publisher's site: https://doi.org/10.1002/1878-0261.13582

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Funding 

Funders who supported this work.

European Research Council (4)

Generalitat Valenciana (1)

Human Frontier Science Program (1)

Instituto de Salud Carlos III (2)

Ministerio de Ciencia e Innovación (4)

Ministerio de Economía y Competitividad (1)

NCI NIH HHS (1)