TWIST2

Overview

TWIST2 encodes a basic helix-loop-helix (bHLH) transcription factor that drives epithelial-to-mesenchymal transition (EMT). TWIST2 promotes invasion and metastasis by repressing E-cadherin and activating mesenchymal gene expression programs. In the context of cancer immunotherapy, TWIST2 upregulation is part of a transcriptional program associated with innate resistance to anti-PD-1 therapy.

Alterations observed in the corpus

  • Mesenchymal-transition transcript up-regulated in pretreatment melanoma tumors that failed to respond to anti-PD-1 therapy; co-enriched within the IPRES (innate anti-PD-1 resistance) transcriptional signature in a 28-sample RNA-seq cohort PMID:26997480.

Cancer types (linked)

  • SKCM / Melanoma: Overexpressed in innately anti-PD-1-resistant pretreatment tumors as part of the IPRES signature PMID:26997480.

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • TWIST2 and the IPRES signature are proposed as candidate transcriptomic biomarkers of innate anti-PD-1 resistance; the IPRES program is enriched across multiple cancer types, suggesting that EMT modulators or anti-angiogenics in combination with checkpoint blockade could overcome this resistance mechanism PMID:26997480.

Open questions

  • The IPRES signature (including TWIST2) is correlative, not causal; whether pharmacologically suppressing TWIST2/IPRES restores anti-PD-1 sensitivity has not been demonstrated PMID:26997480.

Sources

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