ATM-deficient lung, prostate and pancreatic cancer cells are acutely sensitive to the combination of olaparib and the ATR inhibitor AZD6738
Nicholas R. Jette , Suraj Radhamani , Ruiqiong Ye , Yaping Yu , Greydon Arthur , Siddhartha Goutam , Tarek A. Bismar , Mehul Kumar , Pinaki Bose , Steven Yip , Michael Kolinsky , Susan P. Lees-Miller
Genome Instability & Disease ›› 2019, Vol. 1 ›› Issue (4) : 197 -205.
The Ataxia Telangiectasia Mutated (ATM) protein kinase is mutated in several human cancers, presenting potential opportunities for targeted cancer therapy. We previously reported that the poly-ADP-ribose polymerase (PARP) inhibitor olaparib induces transient G2 arrest but not cell death in ATM-deficient lung cancer cells, while the combination of olaparib with the ATM- and Rad3-related (ATR) inhibitor VE-821 induced cell death. Here, we show that combination of olaparib plus the clinically relevant ATR inhibitor AZD6738 also induces cell death in ATM-deficient lung, prostate and pancreatic cancer cells with little effect on their ATM-proficient counterparts. Together, our data suggest that lung, prostate and pancreatic patients whose tumours exhibit loss or inactivation of ATM may benefit from combination of a PARP inhibitor plus an ATR inhibitor.
Cancer Research Society(20229)
Alberta Cancer Foundation(27041)
Engineered Air Chair in Cancer Research(21202)
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