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Association details:
Biomarker:MSH3 mutation
Cancer:Colorectal Cancer
Drug:KU-0060648 (PI3K inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

A Functional Cancer Genomics Screen Identifies a Druggable Synthetic Lethal Interaction between MSH3 and PRKDC

Excerpt:
...subcutaneously engrafted nude mice either with KRAS-driven, MSH3-mutant HCT116 cells [KRASG13D-driven HCT116 [MSH3mut]...we administered 40 mg/kg doses of the DNA-PKcs inhibitor KU60648 twice daily (intraperitoneal injection). Intriguingly, we observed a substantial (final tumor volume, 31.5%) and significant (P = 3.1 × 10−4; Fig. 5A and Supplementary Fig. S10A and S10E) tumor volume shrinkage for HCT116-driven tumors under KU60648 therapy within 14 days...our findings might have direct therapeutic impact on the clinical care of patients suffering from MSH3-mutant MSI colorectal cancer...
DOI:
10.1158/2159-8290.CD-13-0907