Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex

McNamara, Molly C.; Hosios, Aaron M.; Torrence, Margaret E.; Zhao, Ting C.; Fraser, Colin; Wilkinson, Meghan; Kwiatkowski, David J.; Henske, Elizabeth P.; Wu, Chin‐Lee; Sarosiek, Kristopher A.; Valvezan, Alexander J.; Manning, Brendan D.

doi:10.1016/j.isci.2022.105458

Cited by 1 publication

(1 citation statement)

References 69 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FASTIS-associated SASP) or by increasing the expression of specific surface antigens and/or immune checkpoints capable of recruiting/suppressing immune cells. FASTIS in cancer cells may therefore allow the design of a 'one-two punch' strategy, a type of sequential therapy that exploits the concept of collateral sensitivity [224][225][226][227][228][229][230][231][232]. The first therapy approach (FASNi) is not administered with curative intent, but rather to induce a metastable cellular state (senescence) that can be targeted with a second therapy (synthetic lethal) approach (e.g.…”

Section: Exploiting the Acquired Vulnerabilities In Fasnis-induced Do...mentioning

confidence: 99%

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

Menendez,

Cuyàs,

Encinar

et al. 2024

Molecular Oncology

View full text Add to dashboard Cite

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.

show abstract