title: Role of Biomarkers in the Development of PARP Inhibitors.
abstract: Defects in DNA repair lead to genomic instability and play a critical role in cancer development. Understanding the process by which DNA damage repair is altered or bypassed in cancer may identify novel therapeutic targets and lead to improved patient outcomes. Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) has an important role in DNA repair, and novel therapeutics targeting PARP1 have been developed to treat cancers with defective DNA repair pathways. Despite treatment successes with PARP inhibitors (PARPi), intrinsic and acquired resistances have been observed. Preclinical studies and clinical trials in cancer suggest that combination therapy using PARPi and platinating agents is more effective than monotherapy in circumventing drug resistance mechanisms. Additionally, identification of biomarkers in response to PARPi will lead to improved patient selection for targeted cancer treatment. Recent technological advances have provided the necessary tools to examine many potential avenues to develop such biomarkers. This review examines the mechanistic rationale of PARP inhibition and potential biomarkers in their development for personalized therapy.
authors.affiliation: Department of Medicine, Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Bratati
authors.initials: B
authors.lastname: Ganguly
authors.affiliation: Department of Medicine, Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Sonia C
authors.initials: SC
authors.lastname: Dolfi
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Lorna
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.affiliation: Department of Medicine, Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
authors.affiliation: Department of Medicine, Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Hirshfield
keywords: PARP inhibitors; PARP1; biomarkers; personalized therapy