Lung cancer remains the leading cause of cancer incidence and mortality worldwide. Overall our in vitro and in vivo studies showed that PARP inhibitor LT626 acted synergistically with radiation in lung and pancreatic cancers. Using in vivo lung cancer xenograft models we demonstrated that LT626 functioned as an effective radiosensitizer during fractionated radiation treatment, leading to significant decrease in tumor burden and doubling the median survival compared to control group. Combination treatment also increased expression of γH2AX and 53BP1 foci and upregulated expression of phosphorylated ATM, ATR and their respective kinases. Our study demonstrated that combination treatment with LT626 and radiation effectively inhibited growth in lung and pancreatic cancer cell lines, better than individual treatment alone. In this study we examined the effects of the PARP inhibitor LT626 in combination with ionizing radiation in lung and pancreatic cancers. One such class of agents are inhibitors of poly (ADP-ribose) polymerase (PARP). The most relevant addition to radiotherapy regimens are inhibitors of DNA repair and DNA damage response pathways. However, there are many questions on how to optimize its use in chemoradiotherapy. The development of stereotactic body radiation therapy (SBRT) has revolutionized radiation therapy for lung cancers and is an emerging treatment option for pancreatic cancers. Received: NovemAccepted: FebruPublished: February 17, 2017 Ford, email: PARP inhibitor, fractionated radiation, combination therapy, radiosensitizer, lung cancer
Ford 1ġDepartment of Medicine, Division of Oncology, Stanford University, Stanford CA 94305, USAĢDepartment of Biology, Stanford University, Stanford CA 94305, USAģCurrent address: Department of Medicine, Advocate Illinois Masonic Medical Center, Chicago, IL 60657, USAĤVarian Medical Systems, Palo Alto, CA 94306, USA Kedar Hastak 1, Steven Bhutra 2, 3, Renate Parry 4, James M.
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