TDP1 and cancer: Second, multiple PARPi/TOP1i combinations have demonstrated synergy in other cancers [25–30], reflecting both inhibited repair of TOP1i-induced damage as a consequence of PARP trapping [29] and diminished recruitment of the phosphodiesterase TDP1 (Tyrosyl-DNA phosphodiesterase 1) that contributes to reversal of TOP1-DNA covalent complexes [31].