Fatty Acid Synthase Targeting in Oncology

Fatty acid synthase (FASN) is a multi-functional enzyme complex responsible for de novo synthesis of long-chain fatty acids. In many malignancies, enhanced expression and activity of FASN support membrane biogenesis, energy storage and oncogenic signalling. Such metabolic reprogramming underpins tumour growth, survival and metastatic potential. Elevated FASN levels correlate with poorer prognosis in diverse cancers, including breast, colorectal, ovarian and central nervous system tumours. Consequently, FASN has emerged as an attractive therapeutic target, with small-molecule inhibitors designed to disrupt fatty acid synthesis, induce metabolic stress and trigger apoptosis. Preclinical models demonstrate that FASN blockade can reverse chemoresistance, interfere with oncogenic palmitoylation of key receptors and synergise with established agents such as anti-angiogenics or topoisomerase inhibitors. Early clinical investigations of oral FASN inhibitors show manageable safety profiles and promising response signals in refractory tumours. Moreover, modulation of FASN activity influences the tumour microenvironment and antitumour immunity. The global pursuit of FASN-targeted interventions spans fundamental biochemistry to Phase II trials, offering a strategy to exploit cancer’s dependency on lipid metabolism and to augment conventional therapies.

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Fatty Acid Synthase Targeting in Oncology publication trend

The graph below shows the total number of articles in fatty acid synthase targeting in oncology across all publications each year (not limited to Nature Index journals).

Technical terms

Fatty acid synthase (FASN): A multi-enzyme complex that catalyses the de novo synthesis of palmitate from acetyl-CoA and malonyl-CoA.

De novo lipogenesis: The metabolic pathway by which cells convert simple carbon substrates into fatty acids for membrane and energy storage.

S-palmitoylation: A reversible post-translational attachment of palmitic acid to cysteine residues, modulating protein stability and signalling.

Small-molecule inhibitor: A low-molecular-weight compound designed to specifically bind and inhibit the activity of target enzymes such as FASN.

References

1. Targeting ZDHHC21/FASN axis for the treatment of diffuse large B-cell lymphoma. Leukemia (2024).
2. The implications of FASN in immune cell biology and related diseases. Cell Death & Disease (2024).
3. Phase II Investigation of TVB-2640 (denifanstat) with Bevacizumab in Patients with First Relapse High-Grade Astrocytoma. Clinical Cancer Research (2023).
4. Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion. npj Breast Cancer (2024).
5. Fatty Acid Synthase: An Emerging Target in Cancer. Molecules (2020).