bortezomib
Overview
Bortezomib is a first-in-class boronic-acid proteasome inhibitor that reversibly inhibits the 26S proteasome, blocking ubiquitin-mediated protein degradation and inducing apoptosis in tumor cells. It is FDA-approved for multiple myeloma and mantle cell lymphoma. In the sarcoma UCLA patient-derived tumor organoid (PDTO) biobank, it was tested as part of a >400-compound screen and showed subtype-specific sensitivity patterns.
Evidence in the corpus
- In the UCLA sarcoma PDTO biobank (sarcoma_ucla_2024, n=194 specimens, 126 patients across 24 subtypes), chordoma PDTOs were significantly less sensitive to bortezomib than the pan-sarcoma average (p=1.8×10⁻⁵), identifying chordoma as a subtype with relative bortezomib resistance. PMID:39305899
- In n=5 patients who received a treatment regimen matched to their PDTO screen result, one patient received bortezomib + panobinostat; normalized organoid viability correlated with time-to-next-treatment across the matched cohort (R²=0.921, p=0.009). PMID:39305899
- Proteasome inhibitor bortezomib showed broad, highly active anti-tumor effects across all four CTCL cell lines (HH, HUT78, HUT102, SeAX) regardless of genotype, consistent with convergent NFkB activation by CARD11, TNFRSF1B, and PRKG1 mutations in Sézary syndrome PMID:26551667
Resistance mechanisms
- Chordoma (CHDM) demonstrates constitutive proteasome-pathway insensitivity to bortezomib ex vivo; the mechanism driving this differential resistance was not characterized in this study. PMID:39305899
Cancer types (linked)
Sources
- PMID:39305899 — Al Shihabi et al. (Cell Stem Cell 2024). UCLA sarcoma PDTO functional precision-medicine platform; bortezomib subtype sensitivity patterns; chordoma relative resistance.
This page was processed by crosslinker on 2026-05-14. - PMID:26551667
This page was processed by crosslinker on 2026-05-14.