Advances in using PARP inhibitors to treat cancer

Shivaani Kummar; Alice Chen; Ralph E. Parchment; Robert J. Kinders; Jay Ji; Joseph E. Tomaszewski; James H. Doroshow

doi:10.1186/1741-7015-10-25

Advances in using PARP inhibitors to treat cancer

Shivaani Kummar, Alice Chen, Ralph E. Parchment, Robert J. Kinders, Jay Ji, Joseph E. Tomaszewski, James H. Doroshow

Research output: Contribution to journal › Short survey › peer-review

116 Scopus citations

Abstract

The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.

Original language	English (US)
Article number	25
Journal	BMC Medicine
Volume	10
DOIs	https://doi.org/10.1186/1741-7015-10-25
State	Published - Mar 9 2012
Externally published	Yes

Keywords

DNA repair
PARP clinical trials
Synthetic lethality

ASJC Scopus subject areas

General Medicine

Access to Document

10.1186/1741-7015-10-25

Cite this

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title = "Advances in using PARP inhibitors to treat cancer",

abstract = "The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.",

keywords = "DNA repair, PARP clinical trials, Synthetic lethality",

author = "Shivaani Kummar and Alice Chen and Parchment, {Ralph E.} and Kinders, {Robert J.} and Jay Ji and Tomaszewski, {Joseph E.} and Doroshow, {James H.}",

note = "Funding Information: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute.",

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doi = "10.1186/1741-7015-10-25",

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TY - JOUR

T1 - Advances in using PARP inhibitors to treat cancer

AU - Kummar, Shivaani

AU - Chen, Alice

AU - Parchment, Ralph E.

AU - Kinders, Robert J.

AU - Ji, Jay

AU - Tomaszewski, Joseph E.

AU - Doroshow, James H.

N1 - Funding Information: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute.

PY - 2012/3/9

Y1 - 2012/3/9

N2 - The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.

AB - The poly (ADP-ribose) polymerase (PARP) family of enzymes plays a critical role in the maintenance of DNA integrity as part of the base excision pathway of DNA repair. PARP1 is overexpressed in a variety of cancers, and its expression has been associated with overall prognosis in cancer, especially breast cancer. A series of new therapeutic agents that are potent inhibitors of the PARP1 and PARP2 isoforms have demonstrated important clinical activity in patients with breast or ovarian cancers that are caused by mutations in either the BRCA1 or 2 genes. Results from such studies may define a new therapeutic paradigm, wherein simultaneous loss of the capacity to repair DNA damage may have antitumor activity in itself, as well as enhance the antineoplastic potential of cytotoxic chemotherapeutic agents.

KW - DNA repair

KW - PARP clinical trials

KW - Synthetic lethality

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U2 - 10.1186/1741-7015-10-25

DO - 10.1186/1741-7015-10-25

M3 - Short survey

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AN - SCOPUS:84857936584

SN - 1741-7015

VL - 10

JO - BMC Medicine

JF - BMC Medicine

M1 - 25

ER -

Advances in using PARP inhibitors to treat cancer

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

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