▁( though ▁the ▁effect ▁was ▁small ), ▁indicating ▁some ▁degree ▁of ▁synth etic ▁le th ality ▁between ▁ir in ot ec an - indu ced ▁T OP 1 ▁in activ ation ▁and ▁M RE 1 1 ▁def ic iency . ▁ ▁There ▁are ▁a ▁number ▁of ▁pre - cl in ical ▁studies ▁indicating ▁synth etic ▁le th ality ▁of ▁ir in ot ec an ▁with ▁other ▁gen etic ▁or ▁ep igen etic ▁DNA ▁repair ▁def ic ien cies ▁common ▁in ▁can cers . ▁ ▁For ▁instance , ▁the ▁DNA ▁repair ▁gene ▁AT M ▁is ▁frequently ▁hyper m eth yl ated ▁( sil enced ) ▁in ▁many ▁can cers ▁( see ▁hyper m eth yl ation ▁of ▁AT M ▁in ▁can cers ). ▁ ▁A ▁ 2 0 1 6 ▁study ▁showed ▁that ▁low ▁expression ▁of ▁the ▁AT M ▁protein ▁in ▁g astr ic ▁cancer ▁cells ▁in ▁vit ro ▁and ▁in ▁a ▁mouse ▁model ▁caused ▁increased ▁sens itivity ▁to ▁in activ ation ▁by ▁ir in ot ec an ▁compared ▁to ▁cells ▁with ▁high ▁expression ▁of ▁AT M . ▁ ▁This ▁indicates ▁synth etic ▁le th ality ▁of ▁AT M ▁def ic iency ▁with ▁ir in ot ec an - medi ated ▁T OP 1 ▁def ic iency . ▁ ▁Another ▁pre - cl in ical ▁effort ▁was ▁a ▁screen ing ▁study ▁to ▁find ▁a ▁comp ound ▁that ▁would ▁be ▁synth et ically ▁le th al ▁with ▁a ▁def ic iency ▁of ▁N - my c ▁down stream ▁reg ulated ▁gene ▁ 1 ▁( ND