TWIST1
Overview
TWIST1 is a basic helix-loop-helix transcription factor with established roles in epithelial-to-mesenchymal transition (EMT) and cancer metastasis. In small cell lung cancer (SCLC), TWIST1 induction is associated with an acquired chemoresistance expression program, though functional experiments indicate it is a biomarker of resistance rather than a causal driver.
Alterations observed in the corpus
- TWIST1 transcriptionally upregulated in 3/10 SCLC patient-derived xenograft (PDX) models that developed acquired cisplatin/etoposide resistance in vivo; upregulation was accompanied by EMT-like changes including E-cadherin loss PMID:28196596.
- TWIST1 induction and SLFN11 suppression define mutually exclusive resistance programs across 7/10 resistant SCLC PDX models PMID:28196596.
Cancer types (linked)
- SCLC: upregulated in 3/10 PDX models with acquired chemoresistance; pattern is mutually exclusive with SLFN11 silencing PMID:28196596.
Co-occurrence and mutual exclusivity
- Mutually exclusive with SLFN11 downregulation as a resistance mechanism across 7/10 SCLC PDX models PMID:28196596.
Therapeutic relevance
- Functional gain/loss experiments (doxycycline-inducible WT or K145E DNA-binding-mutant TWIST1; shRNA suppression) showed TWIST1 does not change etoposide IC50 in murine SCLC cells, nor reverse EMT markers — authors conclude TWIST1 is a biomarker rather than a direct driver of chemoresistance PMID:28196596.
Open questions
- The 3/10 SCLC PDX models showing TWIST1 induction without SLFN11 loss were not fully characterised; the resistance mechanism in the remaining models (neither TWIST1 nor SLFN11-based) is unknown PMID:28196596.
Sources
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