Homoharringtonine found to bind XPC, impair DNA repair and boost platinum chemotherapy
- A high-content screen for DNA-damage-repair inhibitors (53BP1 foci readout) identified the approved antileukemic drug homoharringtonine.
- It was reported to bind XPC directly, dependent on Thr795, disrupting XPC–damaged DNA binding and impairing nucleotide excision repair and, to a lesser degree, NHEJ.
- Combined with platinum drugs it sensitized tumor cells in vitro and in vivo.
💡 Points Based on the abstract
HHT is a protein-synthesis inhibitor, so reduced XPC or repair-factor levels could be a translation effect rather than direct XPC inhibition; the Thr795 mutant rescue is the key experiment and needs independent replication. Also check exposure: platinum synergy at concentrations reachable in patients, and overlap with HHT's marrow toxicity, decide whether this is more than a cell-line story. A preprint, so not yet peer-reviewed.