Thursday, January 9, 2014
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Cyclin-dependent kinase 12 (CDK12) loss-of-function mutations as
predictors of poly(ADP-ribose) polymerase
(PARP) inhibitor response
In vitro and mouse studies suggest CDK12 mutations could
help predict tumor response to PARP inhibitors. CDK12 mutations have
previously been detected in patients with ovarian cancer. In mice with
ovarian cancer xenografts, CDK12-targeting shRNA combined with the PARP-1 and PARP-2 inhibitor olaparib decreased tumor
volume compared with control shRNA plus olaparib. Next steps include testing
CDK12 as a biomarker in tumor samples from clinical trials of PARP
AstraZeneca plc's olaparib
is in Phase III testing to treat breast cancer early onset (BRCA)-mutant
Tesaro Inc. has the PARP
inhibitor niraparib in Phase III
testing for BRCA-mutant ovarian cancer and breast cancer.
BioMarin Pharmaceutical Inc.
has the PARP inhibitor BMN-673 in Phase III
testing for BRCA-mutant breast cancer.
At least eight other companies have PARP inhibitors in Phase II testing or
earlier for cancer indications.
Published online Jan. 9, 2014
Unpatented; unavailable for
Bajrami, I. et al.
Cancer Res.; published online Nov. 15, 2013;
Contact: Christopher J. Lord, The Institute of Cancer
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