Clinical significance of PARP-1 inhibitors in cancer chemotherapy

Authors

  • Satyakam Singh Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439
  • Dilip Kumar Makwana Analytical Research and Development, Amneal Pharmaceuticals, 50 Horseblock Road, Brookhaven, NY 11719
  • Terrisha Buckley Tuskegee University image/svg+xml
  • Arun Agrawal Internal Medicine, Indiana University Health, Indianapolis, IN 46202
  • Srinivas V Koduru Yale University image/svg+xml
  • Amit K Tiwari Tuskegee University image/svg+xml

DOI:

https://doi.org/10.14259/tcb.v1i1.63

Keywords:

BRCA, DNA repair, PARP inhibitors, breast cancer, ovarian cancer

Abstract

Poly (ADP­ribose) polymerase 1 (PARP-1) protein plays an important role in the repair of single strand breaks (SSBs) in the DNA. This is mediated by base excision repair (BER) of SSBs. PARP-1 inhibition allows accumulation of SSBs and consequently double strand breaks (DSBs). PARP inhibitors disrupt the BER and causes cell damage and death, especially in breast cancer susceptibility          proteins 1 (BRCA 1) or BRCA2­mutated cell in which homologous recombination (HR) pathway is defective. PARP-1 is effective as a single agents in BRCA-1 and BRCA-2 mutated ovarian and breast cancer. In addition, a number of studies have shown beneficial effects with PARP-1 inhibitors in combination with cytotoxic agents that target SSBs, especially in case of triple negative breast cancers (TNBC).  Here we have reviewed potential clinical applications of PARP-1 inhibitors and issues associated with it for successful cancer chemotherapy.

Author Biography

  • Amit K Tiwari, Tuskegee University
    Dr. Amit K. Tiwari received his Pharmacy degree in 2005 from R.I.V.T.E, G.Noida, India and later received his Masters and Ph.D. degree in Pharmacology from Saint John’s University, Queens, NY, USA in the year 2008 and 2011, respectively. He won numerous fellowship awards at St. John’s University including the prestigious University Fellowship in 2010. He finished his Post-Doctoral training at Mount Sinai School of Medicine, NYC, NY, USA in 2011, focusing on Pharmacokinetic/Pharmacodynamic driven anticancer drug development. Dr. Tiwari is currently a Principal Investigator and Assistant Professor in the Department of Biomedical Sciences in CVMNAH, Tuskegee University, Alabama. Dr. Tiwari research is focused in the area of experimental therapeutics to develop novel strategies to combat cancer. He has also extensively characterized the drug resistance mechanism of novel anticancer drugs and has shown ways to improve cancer chemotherapy. Dr. Tiwari long-term research objective is to understand molecular events, biomarkers and signaling pathways that contribute to disparity in cancer progression with the hope of controlling cancer in vulnerable communities. Dr. Tiwari believes that using systems biology approach with the goal of translation to the bedside can develop novel potential therapeutic approaches for the prevention of cancer. Dr. Tiwari is an Editor of VRI Cell Signaling and Journal of Life Sciences. Dr. Tiwari is on the editorial board of over 10 international and national journals including Frontiers in Pharamcology, Analytical Oncology, Journal of Experimental Sciences, Current Clinical Pharmacology etc. Dr. Tiwari serves as a reviewer of over 40 peer-reviewed journals and has extensively published in the field of drug resistance, experimental therapeutics and novel drug development. Dr. Tiwari is often invited and has presented his work at several international conferences. Dr. Tiwari has authored over 30 publications as a research articles, reviews, book chapters and editorial in high impact peer-reviewed journals. 

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Published

2013-10-03

Issue

Vol. 1 No. 1 (2013): First Issue: October, 2013

Section

Mini Reviews