Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines

Pierce, Aisling; McGowan, Patricia M.; Cotter, Maura B.; Mullooly, Maeve; O’Donovan, Norma; Rani, Sweta; O’Driscoll, Lorraine; Crown, John; Duffy, Michael J.

doi:10.4161/cbt.24349

Cited by 38 publications

(31 citation statements)

References 31 publications

(66 reference statements)

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“…Additionally, neratinib was also shown to enhance response when added to mammalian target of rapamycin/phosphatidylinositide 3-kinase inhibitors47 and the PARP inhibitor olaparib 48. These results, as well as those of the study from Seyhan et al28 point to the potential added benefit of using neratinib as a combinational treatment option alongside other targeted treatments as well as conventional chemotherapeutics.…”

Section: Introductionmentioning

confidence: 84%

Profile of neratinib and its potential in the treatment of breast cancer

Feldinger

Kong²

2015

BCTT

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The HER (ErbB) receptor tyrosine kinase receptors are implicated in many cancers and several anti-HER treatments are now approved. In recent years, a new group of compounds that bind irreversibly to the adenosine triphosphate binding pocket of HER receptors have been developed. One of these compounds, neratinib, has passed preclinical phases and is currently undergoing various clinical trials. This manuscript reviews the preclinical as well as clinical data on neratinib. As a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib has been shown to be effective against HER2-overexpressing or mutant tumors in vitro and in vivo. Neratinib is currently being investigated in various clinical trials in breast cancers and other solid tumors, including those with HER2 mutation. Earlier studies have already shown promising clinical activity for neratinib. However, more translational research is required to investigate biomarkers that could help to predict response and resistance for selection of appropriate patients for treatment with neratinib, either as monotherapy or in combination with other drug(s).

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Section: Introductionmentioning

confidence: 84%

Profile of neratinib and its potential in the treatment of breast cancer

Feldinger

Kong²

2015

BCTT

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“…Five of the sporadic BLC cell lines (MDA MB 231, MDA MB 468, BT20, HCC1143, and HS578T), one of the BRCA1 mutant lines (HCC1937), and the three non-BLC cell lines (MCF7, SKBR3, and T47D) tested in our work were assayed in the PARP study (65). The results are difficult to interpret without comparing the lines to a normal breast control cell line, but there was no uniformity in PARP inhibitor sensitivity among the different subtypes from these data (65). Thus, on the basis of that work, it also appears that not all BRCA1 mutant genotypes and breast tumor subtype designations are effective predictors of sensitivity to PARP inhibitors.…”

Section: Discussionmentioning

confidence: 99%

“…However, sporadic BLCs have failed after treatment with single agents (62,64) and PARP inhibitor/antiangiogenic therapy combinations (63). We did not test our entire cell line panel for PARP inhibitor sensitivity, because most of the cell lines, along with others representing different subtypes, have already been tested for sensitivity to two different PARP inhibitors (65). Five of the sporadic BLC cell lines (MDA MB 231, MDA MB 468, BT20, HCC1143, and HS578T), one of the BRCA1 mutant lines (HCC1937), and the three non-BLC cell lines (MCF7, SKBR3, and T47D) tested in our work were assayed in the PARP study (65).…”

Section: Discussionmentioning

confidence: 99%

“…We did not test our entire cell line panel for PARP inhibitor sensitivity, because most of the cell lines, along with others representing different subtypes, have already been tested for sensitivity to two different PARP inhibitors (65). Five of the sporadic BLC cell lines (MDA MB 231, MDA MB 468, BT20, HCC1143, and HS578T), one of the BRCA1 mutant lines (HCC1937), and the three non-BLC cell lines (MCF7, SKBR3, and T47D) tested in our work were assayed in the PARP study (65). The results are difficult to interpret without comparing the lines to a normal breast control cell line, but there was no uniformity in PARP inhibitor sensitivity among the different subtypes from these data (65).…”

Section: Discussionmentioning

confidence: 99%

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BRCA1 Pathway Function in Basal-Like Breast Cancer Cells

Hill

Clark

Silver

et al. 2014

Molecular and Cellular Biology

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c Sporadic basal-like cancers (BLCs) are a common subtype of breast cancer that share multiple biological properties with BRCA1-mutated breast tumors. Despite being BRCA1 ؉/؉ , sporadic BLCs are widely viewed as phenocopies of BRCA1-mutated breast cancers, because they are hypothesized to manifest a BRCA1 functional defect or breakdown of a pathway(s) in which BRCA1 plays a major role. The role of BRCA1 in the repair of double-strand DNA breaks by homologous recombination (HR) is its best understood function and the function most often implicated in BRCA1 breast cancer suppression. Therefore, it is suspected that sporadic BLCs exhibit a defect in HR. To test this hypothesis, multiple DNA damage repair assays focused on several types of repair were performed on a group of cell lines classified as sporadic BLCs and on controls. The sporadic BLC cell lines failed to exhibit an overt HR defect. Rather, they exhibited defects in the repair of stalled replication forks, another BRCA1 function. These results provide insight into why clinical trials of poly(ADP-ribose) polymerase (PARP) inhibitors, which require an HR defect for efficacy, have been unsuccessful in sporadic BLCs, unlike cisplatin, which elicits DNA damage that requires stalled fork repair and has shown efficacy in sporadic BLCs.

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“…A Phase III trial statistics for this combination predicted a probability of success of 90% 41. Combined treatment with olaparib and either the CDK1 inhibitor (RO-3306) or a pan HER inhibitor (neratinib, afatinib) resulted in superior growth inhibition compared to that obtained with olaparib alone 40. Although better patient stratification is likely to improve therapeutic outcome, several PARP inhibitor resistance mechanisms in BRCA-associated tumors have been proposed 42.…”

Section: The Target and The Treatment Of Tnbcmentioning

confidence: 99%

Novel therapeutic strategies for patients with triple-negative breast cancer

Zhang¹,

Liu²,

Wang³

et al. 2016

OTT

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Triple-negative breast cancer (TNBC) represents a very heterogeneous group of breast diseases. Currently, the backbone of therapy for TNBC is mainly chemotherapy as there are no effective specific targeted agents approved to treat TNBC. Despite initial responses to chemotherapy, resistance frequently and rapidly develops and metastatic TNBC has a poor prognosis. Therefore, new targeted strategies are, accordingly, urgently needed. This article discusses the recent developments in targeted agents explored for TNBC, aiming to offer novel therapeutic strategies that can potentially assist in designing personalized therapeutics in the future as well as provide the basis for further research in an attempt to target TNBC.

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Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines

Abstract: Comparative antiproliferative effects of iniparib and olaparib on a panel of triple-negative and non-triple-negative breast cancer cell lines, Cancer Biology & Therapy, 14:6, 537-545,

Cited by 38 publications

References 31 publications

Profile of neratinib and its potential in the treatment of breast cancer

Profile of neratinib and its potential in the treatment of breast cancer

BRCA1 Pathway Function in Basal-Like Breast Cancer Cells

Novel therapeutic strategies for patients with triple-negative breast cancer

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