Lung
Treatments
Veliparib
Author: Y. Albert Yeh, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 1 April 2021
Last staff update: 11 June 2021
Copyright: 2020-2024, PathologyOutlines.com, Inc.
PubMed Search: Veliparib[TI] free full text[SB]
Table of Contents
Definition / general | Trade name | Indications | Pathophysiology | Diagrams / tables | Clinical information | Uses by pathologists | Side effects | Drug administration | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Yeh YA. Veliparib. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungveliparib.html. Accessed April 25th, 2024.
Definition / general
- A poly (ADP-ribose) polymerase (PARP) inhibitor blocks PARP1 and PARP2, thereby preventing repair of DNA damage
- Developed by Abbvie
- Synonym: ABT-888, 912444-00-9, CHEBI:62880, 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide, veliparib
Trade name
- Veliparib®
Indications
- In 2016, U.S. Food and Drug Administration awarded orphan drug designation for treating advanced squamous cell carcinoma of lung (FDA: Search Orphan Drug Designations and Approvals [Accessed 17 July 2020])
Pathophysiology
- Base excision repair and homologous recombination mediated double strand breaks system responsible for the repair of damaged DNA (Figure 1, panel A)
- In cells with BRCA1/2 mutated cells, base excision repair and other DNA repair mechanisms compensate for the nonfunctional homologous recombination (Figure 1, panel B)
- In cells with nonfunctioning base excision repair because of PARP1 inhibition, at least one copy of BRCA1/2 with functioning homologous recombination can repair the damaged DNA (Figure 1, panel C)
- In mutated BRCA1/2 cancer cells, PARP inhibitors prevents the base excision repair leading to cell death (Figure 1, panel D)
- Reference: Mod Pathol 2020;33:944, see diagram below
Clinical information
- Phase II clinical trials for treating metastatic melanoma, breast cancer, non small cell lung cancer, castration resistant prostate cancer and pancreatic ductal adenocarcinoma (ClinicalTrials: Veliparib - List Results [Accessed 17 July 2020])
- Phase III ongoing clinical trials to treat non small cell lung cancer, triple negative BRCA breast cancer, advanced ovarian cancer and glioblastoma (ClinicalTrials: Veliparib - List Results [Accessed 17 July 2020])
- Clinical trials of chemotherapeutics in combination with doxorubicin, temozolomide, topotecan, carboplatin, paclitaxel, pemetrexed, cyclophosphamide, gemcitabine for treating advanced myeloproliferative disorders, acute myeloid leukemia, metastatic pancreatic cancer, locally advanced rectal cancer (National Cancer Institute: Clinical Trials Using Veliparib [Accessed 17 July 2020])
Uses by pathologists
- None at this time
Side effects
- Gastrointestinal: nausea, vomiting
- Fatigue
- Myelosuppression (anemia, neutropenia, thrombocytopenia)
- Secondary leukemia and myelodysplastic syndrome (late serious effects)
- Reference: Onco Targets Ther 2015;8:1931
Drug administration
- Drug taken by mouth
Additional references
Board review style question #1
- Veliparib is a potential therapeutic agent inhibiting which of the following proteins?
- BRAF
- BRCA1 and BRCA2
- PARP1 and PARP2
- TP53
Board review style answer #1
