Forkhead box protein A1 (FOXA1) (FOXA1)

Forkhead box protein A1 (FOXA1) is a pioneering transcription factor essential for the recruitment of nuclear receptors to specific genomic loci (UniProt P55317). By binding to compacted chromatin through its winged-helix DNA-binding domain, FOXA1 facilitates the opening of chromatin, allowing for the subsequent binding of the estrogen receptor (ER) in breast cancer and the androgen receptor (AR) in prostate cancer (Jozwik & Carroll, 2012, Nature Reviews Cancer). This makes FOXA1 a master regulator of hormone-driven oncogenic programs and a key mediator of resistance to standard endocrine and anti-androgen therapies (Adams et al., 2019, Nature). Because transcription factors are historically difficult to target with small molecules, therapeutic strategies have shifted toward targeting FOXA1 mRNA using antisense oligonucleotides (ASOs) or RNA interference (RNAi) to induce transcript degradation and reduce protein expression (Parolia et al., 2019, Cancer Cell). Successful depletion of FOXA1 has been shown to inhibit tumor growth and restore sensitivity to hormone therapies in preclinical models, positioning it as a high-priority target in refractory solid tumors.

Other names

Hepatocyte nuclear factor 3-alphaHNF-3-alphaHNF3ATCF3ATranscription factor 3A

Degradation of FOXA1 mRNA via antisense oligonucleotides or RNA interference to prevent translation of the pioneer transcription factor.