Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas - PubMed
5 hours ago
- #metabolic reprogramming
- #B-cell lymphoma
- #PARP inhibitor
- L-asparaginase (ASNase) induces metabolic reprogramming in B-cell lymphomas (BCL), increasing de novo serine biosynthesis via phosphoglycerate dehydrogenase (PHGDH).
- ASNase-treated cells show replication stress and heightened poly(ADP-ribose) polymerase (PARP) activity, indicating reliance on DNA repair mechanisms.
- Combining ASNase with PARP inhibitor Olaparib enhances anti-tumor effects in BCL models and shows potential in homologous recombination-proficient colorectal cancer.
- The study identifies metabolic and genomic vulnerabilities in ASNase-treated tumors, supporting a combination therapy approach with clinically approved drugs.