2021
DOI: 10.3389/fmolb.2021.633344
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Veliparib Is an Effective Radiosensitizing Agent in a Preclinical Model of Medulloblastoma

Abstract: Medulloblastoma is the most common malignant childhood brain tumor, and 5-year overall survival rates are as low as 40% depending on molecular subtype, with new therapies critically important. As radiotherapy and chemotherapy act through the induction of DNA damage, the sensitization of cancer cells through the inhibition of DNA damage repair pathways is a potential therapeutic strategy. The poly-(ADP-ribose) polymerase (PARP) inhibitor veliparib was assessed for its ability to augment the cellular response to… Show more

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Cited by 11 publications
(10 citation statements)
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“…130 It was observed a single dose of veliparib in combination with IR significantly augmented intratumoral apoptosis on immunohistochemistry staining, signifying that veliparib augmented IR induced MB cell death in vivo. 130 Notably, knockout of RBM5-AS1 triggered sensitization of DAOY xenograft tumors to IR, which was associated with augmented apoptosis. 51 Thus, RBM5-AS1 is a promising target to mitigate radioresistance in MB via apoptosis.…”
Section: Irradiation Induce Apoptosis Therapeutic Mechanismsmentioning
confidence: 92%
See 1 more Smart Citation
“…130 It was observed a single dose of veliparib in combination with IR significantly augmented intratumoral apoptosis on immunohistochemistry staining, signifying that veliparib augmented IR induced MB cell death in vivo. 130 Notably, knockout of RBM5-AS1 triggered sensitization of DAOY xenograft tumors to IR, which was associated with augmented apoptosis. 51 Thus, RBM5-AS1 is a promising target to mitigate radioresistance in MB via apoptosis.…”
Section: Irradiation Induce Apoptosis Therapeutic Mechanismsmentioning
confidence: 92%
“…Interestingly, interfering with the Ptch1/SMO/SUFU/GLI axis in the hedgehog pathway with small molecules has been implicated as a promising therapy for SHH MBs via apoptosis 27 . Remarkably, veliparib was tested as a radiosensitizing agent in both in vitro and a mouse model of MB 130 . It was observed a single dose of veliparib in combination with IR significantly augmented intratumoral apoptosis on immunohistochemistry staining, signifying that veliparib augmented IR induced MB cell death in vivo 130 …”
Section: Irradiation Induce Apoptosis Therapeutic Mechanismsmentioning
confidence: 99%
“…Thus, it will be interesting to see whether non-WNT/non-SHH patients will be included in currently running trials using PARP inhibitors (NCT03233204 and NCT04236414). Lastly, several preclinical studies with different compounds indicate that the concept of sensitizing cancer cells to radiotherapy using small molecules could be potentially interesting for non-WNT/non-SHH MB [165][166][167]…”
Section: Other Molecular Therapeutic Approachesmentioning
confidence: 99%
“…Similarly, the U.S. FDA approved rucaparib as a single agent for treating relapsed ovarian cancer with mutations in BRCA genes in patients who had received two or more lines of chemotherapy [ 74 ]. Unlike the other PARP inhibitors, veliparib has not shown anti-proliferative activity, but radio and chemo-sensitizing effects were reported in cancer cells [ 75 ].…”
Section: Current Therapies For Epithelial Ovarian Cancermentioning
confidence: 99%