Table 3 Preclinical studies of niraparib on different cancer models

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

[66]

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

[67]

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

[68]

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

[50]