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Table 3 Preclinical studies of niraparib on different cancer models

From: PARP inhibitors as potential therapeutic agents for various cancers: focus on niraparib and its first global approval for maintenance therapy of gynecologic cancers

Study characteristics Methods Primary outcomes observed References
Panel of 25 TNBC PDX models in mice Gapped sequential design (cyclophosphamide followed by niraparib after 14 days)
investigating the antitumor efficacy of niraparib alone or in combination with alkylating agent, cyclophosphamide (standard chemotherapy of TNBC)
- Cyclophosphamide showed partial to complete tumor regression
- For niraparib, significant antitumor response occurs with BRCA mutations or a high HRD score
- Potentiation with inhibition of tumor relapse after discontinuing cyclophosphamide (in niraparib sensitive tumor sub types)
- In niraparib responder cells, superior efficacy compared to sequential therapy of cyclophosphamide alone
Panel of 17 BBC PDXmodels in mice - Experimental design in which groups were treated with niraparib (50 mg/kg/day) and vehicle control separately
- 13 of BBC were TNBC cells
- Treatment continued for 28 days
- Tumor volume and body weight measurements
- No sign of body weight reduction relative to the vehicle control
- Niraparib exhibited robust efficacy in five of the 17 models. All five responsive models were TNBC
- Niraparib is generally effective in subset of TNBC patients
Four neuroblastoma cell lines (in vitro) and a murine xenograft model of metastatic neuroblastoma (in vivo) - Clonogenic survival assays
- ELISA (PARP assay)
Poly ADP
- Immunohistochemistry
Measurement of cleaved caspase-3, γ-H2AX, and Ki67
- Reduced clonogenicity
- Additive effects with radiation
- Significantly prolonged survival in combined modalities
- ↑cleaved caspase-3 and γ-H2AX
Tumor cell lines derived from lung, breast, and prostate cancers (MDA-MB-231, LnCaP, MDA-MB-436, CCD-16, and MCF-10A cells) plus normal cell lines - Clonogenic survival analyses - μM conc of niraparib radiosensitized tumor cell lines independently of their p53 status but not cell lines derived from normal tissues.
- It also sensitized tumor cells to H2O2
  1. Abbreviations: TNBC triple negative breast cancer, ADP adenosine diphosphate, ELISA enzyme linked immunosorbet assay, HRD homologous recombination deficiency, PDX patient derived xenograft, BBC basal breast cancer,  increased