Anticancer Chemosensitization and Radiosensitization by the Novel Poly(ADP-ribose) Polymerase-1 Inhibitor AG14361

Calabrese, Christopher; Almassy, Robert J.; Barton, Stephanie; Batey, Michael A.; Calvert, A. Hilary; Canan-Koch, Stacie; Durkacz, Barbara W.; Hostomský, Zdeněk; Kumpf, Robert A.; Kyle, Suzanne; Li, Jianke; Maegley, Karen A.; Newell, David R.; Notarianni, Elena; Stratford, Ian J.; Skalitzky, Donald J.; Thomas, Huw D.; Wang, Lan-Zhen; Webber, S. E.; Williams, Kaye J.; Curtin, Nicola J.

doi:10.1093/jnci/djh005

Cited by 445 publications

(384 citation statements)

References 52 publications

Supporting

Mentioning

358

Contrasting

Unclassified

Order By: Relevance

“…studies demonstrated that a variety of PARP inhibitors enhance the antiproliferative and cytotoxic effects of topo I poisons (23)(24)(25)(26)(27)(28)(29)(30)(31). Consistent with those earlier studies, we observed that treating various solid tumor cell lines, including A2780, SKOV3, Ovcar5, and A549 cells, with the PARP inhibitor veliparib (78) sensitized cells to the topo I poison topotecan (Fig.…”

Section: Parp Inhibition Sensitizes Cells To Topo I Poisons-previoussupporting

confidence: 90%

See 1 more Smart Citation

Enhanced Killing of Cancer Cells by Poly(ADP-ribose) Polymerase Inhibitors and Topoisomerase I Inhibitors Reflects Poisoning of Both Enzymes

Patel

Flatten

Schneider

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: PARP inhibitors and topoisomerase I poisons (Top1p) synergize by an unknown mechanism. Results: Although Parp1 deletion fails to increase Top1p sensitivity, transfection with catalytically inactive PARP1 or its isolated DNA binding domain does sensitize. Conclusion: PARP inhibitors poison PARP1 to diminish repair of topoisomerase I-triggered DNA damage. Significance: These results predict that tumors with elevated PARP1 will be particularly sensitive to Top1p/PARP inhibitor combinations.

show abstract

Section: Parp Inhibition Sensitizes Cells To Topo I Poisons-previoussupporting

confidence: 90%

“…A number of previous studies have demonstrated that small molecule PARP inhibitors selectively sensitize cells to topo I poisons in vitro and in vivo (23)(24)(25)(26)(27)(28)(29)(30)(31)(32). At least three explanations have been advanced to explain these observations.…”

mentioning

confidence: 99%

Enhanced Killing of Cancer Cells by Poly(ADP-ribose) Polymerase Inhibitors and Topoisomerase I Inhibitors Reflects Poisoning of Both Enzymes

Patel

Flatten

Schneider

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Chemo-and radiosensitization by PARP inhibition has been the subject of many reviews (Haince et al, 2005;Plummer, 2006;Plummer and Calvert, 2007;Ratnam and Low, 2007;Lord and Ashworth, 2008). A review of the original research reports indicates that although chemo-and radiotherapy can synergize with PARP inhibitors (PARPi), the assessment of the resulting cellular responses may be limited if clonogenic survival or growth inhibition are chosen as end points (Calabrese et al, 2003(Calabrese et al, , 2004Curtin et al, 2004).…”

Section: Arrest/senescencementioning

confidence: 99%

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

et al. 2010

View full text Add to dashboard Cite

“…Inhibitors of PARP improve the efficiency and selectivity of DNA-damaging agents (Calabrese et al 2004). The PARP inhibitors olaparib and rucaparib have entered clinical trials for several cancer types, either as monotherapy or in combination with cytotoxic drug therapy Tutt et al 2010;Plummer et al 2013;Bendell et al 2015;Mateo et al 2015;Drew et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

Rae

Mairs

2016

International Journal of Radiation Biology

View full text Add to dashboard Cite

Purpose: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro the potential benefit to be gained by combining radiation treatment with cytotoxic drugs. Materials and methods: Inhibitors of DNA repair and heat shock protein 90 and an inducer of oxidative stress were evaluated in combination with X-radiation for their capacity to reduce clonogenic survival and delay the growth of multicellular tumor spheroids. Results: Inhibitors of the PARP DNA repair pathway, olaparib and rucaparib, and the HSP90 inhibitor 17-DMAG, enhanced the clonogenic cell kill and spheroid growth delay induced by X-radiation. However, the oxidative stress-inducing drug elesclomol failed to potentiate the effects of X-radiation. PARP inhibitors arrested cells in the G 2 /M phase when administered as single agents or in combination with radiation, whereas elesclomol and 17-DMAG did not affect radiation-induced cell cycle modulation. Conclusion: These results indicate that radiotherapy of prostate cancer may be optimized by combination with inhibitors of PARP or HSP90, but not elesclomol. ARTICLE HISTORY

show abstract

Anticancer Chemosensitization and Radiosensitization by the Novel Poly(ADP-ribose) Polymerase-1 Inhibitor AG14361

Abstract: AG14361 is, to our knowledge, the first high-potency PARP-1 inhibitor with the specificity and in vivo activity to enhance chemotherapy and radiation therapy of human cancer.

Cited by 445 publications

References 52 publications

Enhanced Killing of Cancer Cells by Poly(ADP-ribose) Polymerase Inhibitors and Topoisomerase I Inhibitors Reflects Poisoning of Both Enzymes

Enhanced Killing of Cancer Cells by Poly(ADP-ribose) Polymerase Inhibitors and Topoisomerase I Inhibitors Reflects Poisoning of Both Enzymes

Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

Contact Info

Product

Resources

About