Abstract: The present invention provides a barcoded exon tagging and gene disruption platform to create barcoded control, heterozygous gene knockout (KO) and homozygous gene KO panels of diploid human cells for high-throughput, multiplexed genotoxin screens.

Abstract: Described herein is the finding that polymerase ? (Pol?) and N-methylpurine DNA glycosylase (MPG) can be used as biomarkers to evaluate the sensitivity of a subject to combination therapy that includes treatment with either temozolomide (TMZ) and methoxyamine, or TMZ and a poly(ADP-ribose) polymerase (PARP) inhibitor. Thus, provided herein is a method of determining if a subject will be sensitive to TMZ and methoxyamine, or TMZ and a PARP inhibitor by measuring expression of Pol? and MPG in a sample from the subject and comparing expression of Pol? and MPG in the sample to a control. A decrease in expression of Pol? and an increase in expression of MPG relative to the control indicates the subject is sensitive to TMZ and methoxyamine, or sensitive to TMZ and the PARP inhibitor.

Abstract: Described herein is the finding that polymerase ? (Pol?) and N-methylpurine DNA glycosylase (MPG) can be used as biomarkers to evaluate the sensitivity of a subject to combination therapy that includes treatment with either temozolomide (TMZ) and methoxyamine, or TMZ and a poly(ADP-ribose) polymerase (PARP) inhibitor. Thus, provided herein is a method of determining if a subject will be sensitive to TMZ and methoxyamine, or TMZ and a PARP inhibitor by measuring expression of Pol? and MPG in a sample from the subject and comparing expression of Pol? and MPG in the sample to a control. A decrease in expression of Pol? and an increase in expression of MPG relative to the control indicates the subject is sensitive to TMZ and methoxyamine, or sensitive to TMZ and the PARP inhibitor.

Abstract: The invention provides anticancer methods. In one embodiment, the inventive method involves the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an inhibitor of DNA polymerase beta. In another embodiment, the invention provides anticancer methods involving the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an siRNA or shRNA in an amount sufficient to attenuate base excision repair within the cell. Another aspect of the invention relates to pharmaceutical compositions comprising an siRNA or shRNA that attenuates base excision repair.

Abstract: The invention provides anticancer methods. In one embodiment, the inventive method involves the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an inhibitor of DNA polymerase beta. In another embodiment, the invention provides anticancer methods involving the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an siRNA or shRNA in an amount sufficient to attenuate base excision repair within the cell. Another aspect of the invention relates to pharmaceutical compositions comprising an siRNA or shRNA that attenuates base excision repair.