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Twist-related protein 1 (TWIST1) is a **basic helix–loop–helix (bHLH) transcription factor** encoded by the *TWIST1* gene. It binds specific DNA sequences to regulate gene activity crucial for embryonic development, cell proliferation, differentiation, and mesodermal lineage specification, especially in craniofacial and limb formation[2][3][6]. TWIST1 plays a central role in **cancer progression and metastasis** by promoting epithelial-to-mesenchymal transition (EMT), enhancing cell motility, and contributing to chemotherapy resistance and cancer stem cell maintenance[3][4]. High TWIST1 expression is associated with poor prognosis in multiple cancer types. TWIST1 also influences tissue fibrosis by regulating TGF-β/Smad signaling[1]. Mutations in *TWIST1* are linked to developmental disorders such as **Sweeney-Cox syndrome** and **isolated craniosynostosis**. As a transcriptional regulator of many genes involved in differentiation, proliferation, and stemness, TWIST1 is an attractive but challenging **therapeutic target** for cancer and fibrotic diseases[3][4][1].
Inhibitors aim to suppress TWIST1 expression or activity, often by interfering with upstream signaling pathways (e.g., Akt, MAPK, STAT3), modulating transcriptional activity via noncoding RNAs (microRNAs, lncRNAs), or using RNA interference to block TWIST1 translation[3][4][5].
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