SPEN inactivation drives resistance to androgen receptor pathway inhibitors in metastatic prostate cancer
A newly discovered resistance mechanism to prostate cancer drugs appears in one in thirty patients after treatment, helping doctors anticipate when therapy might stop working.
A genome-wide loss-of-function screen identified SPEN inactivation as a top driver of enzalutamide resistance in prostate cancer, subsequently validated in 6,828 real-world mCRPC patients showing SPEN mutations enriched from 2.1% to 3.6% after ARPI therapy with TTNT HR=2.67. This novel resistance mechanism, confirmed across rapid autopsy tissue microarrays, has direct implications for ARPI treatment selection in metastatic castration-resistant prostate cancer.
What the study was
- Study design
- multimodal_genomic_and_real_world_cohort
- Population
- Metastatic castration-resistant prostate cancer patients
- Sample size
- 6828
- Category
- Genomics/Precision Medicine
- Maturity
- Validated
- Journal
- Clinical Cancer Research
Why it surfaced
Novel resistance gene discovery (genome-wide screen) validated at population scale (n=6,828 FoundationOne database); high novelty for T5 precision oncology; directly actionable for ARPI treatment selection in mCRPC
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