The Emerging Role of Poly (ADP-Ribose) Polymerase Inhibitors as Effective Therapeutic Agents in Renal Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34307148", "kind": "science-record", "revision": 8, "content_hash": "sha256:55602631ae54b9b9c87408adacadd5edee07bd4119f8610cff49155a6f520008", "created_at": "2026-11-01T15:41:45Z", "updated_at": "2026-11-01T22:47:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Emerging Role of Poly (ADP-Ribose) Polymerase Inhibitors as Effective Therapeutic Agents in Renal Cell Carcinoma.", "doi": "10.3389/fonc.2021.681441", "pmid": "34307148", "authors": ["Jerred P Pletcher", "Sayani Bhattacharjee", "Jonathan P Doan", "Rebecca Wynn", "Puneet Sindhwani", "Nagalakshmi Nadiminty", "Firas G Petros"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "Renal cell carcinoma (RCC) is the sixth most common cancer in the US. However, no significant changes in management have occurred since the tyrosine kinase era until the recent breakthrough with checkpoint inhibitors. Therefore, the need for more therapeutic options is paramount. Our objective was to determine whether PARP inhibition represents a novel therapeutic option for RCC. We used publicly available COSMIC, GDC Data Portal, and cBioPortal databases to explore mutations in DNA repair genes in RCC tissues from the TCGA cohort. We treated a human normal renal epithelial cell line RPTEC/TERT1 and two human renal cancer cell lines ACHN and CAKI-2 with PARPi niraparib, olaparib, rucaparib, veliparib, and talazoparib. Cell survival, cell proliferation, clonogenic ability, and apoptosis were assessed. RCC xenografts in SCID mice were treated with PARPi to evaluate their efficacy in vivo. Data mining revealed that ~27-32% of RCC tissues contain mutations in homologous recombination genes. Niraparib and talazoparib were the most effective at reducing cell survival, proliferation, and clonogenic ability in vitro. Niraparib, talazoparib, and rucaparib were the most effective in reducing RCC xenograft growth in vivo. Agents such as PARPi that exploit mutations in DNA damage repair genes may be effective therapeutic options for RCC.", "claims": [{"id": "claim-method", "statement": "Multiple group comparison was performed by one-way ANOVA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34307148", "locator": "sections[11] \"Statistical Analyses\" paragraph 2", "quote": "Multiple group comparison was performed by one-way ANOVA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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"RNF4", "HELQ"], ["BARD1", "NUDT1", "TREX2", "UBE2V2", "RDM1"], ["WRN", "DUT", "APTX", "UBE2N", "NABP2"], ["BUB1", "RRM2B", "SPO11", "H2AFX", "ATRIP"], ["CENPE", "POLG", "ENDOV", "CHAF1A", "MDC1"], ["ZW10", "REV3L", "UBE2A", "SETMAR", "RAD1"], ["TTK", "MAD2L2", "UBE2B", "RECQL4", "RAD9A"], ["KNTC1", "REV1", "RAD18", "MPLKIP", "HUS1"], ["RAD17", "TP53BP1", "CLK2", "", ""], ["TP53", "TOPBP1", "PER1", "", ""]], "row_count": 42, "column_count": 5, "numeric_cells": 131, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:34307148:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:67789d9c0e919107e8e175c19a9ef02ccafbdf4ef81efde8543bc03d84e10561", "bytes": 1204, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T2", "version": null, "note": "COSMIC, GDC Data Portal, and cBioPortal were used to explore the rate of mutations in direct and indirect DNA repair genes in RCC tissues from the TCGA cohort.", "structure": {"pmcid": "PMC8300201", "section_index": 13, "section_title": "RCC Tissues Harbor Mutations in Several Direct and Indirect DNA Damage Repair Genes", "row_count": 27, "column_count": 4}, "table": {"label": "Table 2", "caption": "COSMIC, GDC Data Portal, and cBioPortal were used to explore the rate of mutations in direct and indirect DNA repair genes in RCC tissues from the TCGA cohort.", "rows": [["Direct and Indirect DNA repair Genes", "COSMIC", "GDC Data Portal", "cBioPortal"], ["VHL", "39.97%", "27.15%", "21.3%"], ["PBRM1", "23.50%", "23.21%", "20.5%"], ["TTN", "9.03%", "22.48%", "0"], ["MUC4", "2.24%", "12.85%", "0"], ["SETD2", "9.14%", "9.49%", "8.4%"], ["MUC16", "5.43%", "9.20%", "0.1%"], ["BAP1", "8.88%", "7.45%", "6.4%"], ["DST", "2.24%", "6.86%", "0"], ["KMT2C", "3.04%", "6.57%", "4.3%"], ["LRP2", "2.46%", "6.42%", "2.8%"], ["MACF1", "1.73%", "5.84%", "0"], ["TP53", 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RCC xenografts in SCID mice w", "material Supplementary Figure 1PARPi induced apoptosis in RCC cells. RPTEC/TERT1, ACHN, and Caki-2", "olaparib, rucaparib, and talazoparib induced apoptosis in RCC cells.Click here for additional data", "aterials Supplementary Figure 1PARPi induced apoptosis in RCC cells. RPTEC/TERT1, ACHN, and Caki-2"], "order_basis": "paper_text_order:861", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ptosis were assessed. RCC xenografts in SCID mice were treated with PARPi to evaluate their efficac", "reated with PARPi to evaluate their efficacy in vivo. Data mining revealed that ~27-32% of RCC ti", "t effective in reducing RCC xenograft growth in vivo. 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