Rare histologic transformation of a CTNNB1 (β-catenin) mutated prostate cancer with aggressive clinical course
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View abstract on PubMed
Summary
This summary is machine-generated.This study details a rare CTNNB1-mutated prostate cancer case with aggressive progression. Current treatments were ineffective, highlighting the need for new therapies targeting rare molecular subtypes.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- Genomic alterations in CTNNB1 (Cadherin-Associated Protein), Beta 1 are uncommon in prostate cancer (PCa).
- CTNNB1 mutations can cause Wnt/β-catenin pathway hyperactivation, driving PCa progression and treatment resistance.
- Targeted therapies for Wnt/β-catenin-driven PCa remain limited.
Purpose Of The Study
- To report a rare case of histologic transformation in CTNNB1-mutated metastatic castration-resistant prostate cancer (mCRPC).
- To characterize the aggressive clinical course and molecular features of this rare PCa subtype.
- To evaluate therapeutic sensitivities using patient-derived models.
Main Methods
- Histological and molecular characterization of liver metastases from a CTNNB1-mutated mCRPC patient.
- Generation of patient-derived organoids (PDOs) and patient-derived xenografts (PDXs).
- Drug response assays on PDOs and PDXs to assess sensitivity to various agents.
Main Results
- The tumor exhibited double-negative CRPC characteristics with nuclear β-catenin expression and keratin 7 positivity.
- Lack of sensitivity to standard mCRPC treatments (enzalutamide, docetaxel) was observed.
- Limited activity of CK1 and tankyrase inhibitors; PDOs showed insensitivity to SMARCA2/4-targeting PROTACs.
Conclusions
- This CTNNB1-mutated mCRPC case presents diagnostic challenges for double-negative CRPC.
- The findings underscore the need for translational research to develop targeted treatments for rare PCa molecular subtypes.
- Effective therapeutic strategies for this aggressive PCa variant are currently lacking.
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