{"doi":"10.1007/s12609-025-00582-5","title":"Targeting PARP1: A Promising Approach for Next-Generation Poly (ADP-ribose) Polymerase Inhibitors","abstract":"Limitations of Poly ADP‒ribose Polymerase PARP Inhibitors: PARPis have demonstrated efficacy in BRCA-mutated cancers deficient in homologous recombination repair. Furthermore, PARPis have shown efficacy in BRCA-wild-type cancers with a homologous recombination deficiency phenotype known as BRCAness. Current clinically approved PARPis inhibit both PARP1 and PARP2, and their clinical promise is limited by toxicity, resistance, and a lack of combination partners. Recent Findings: PARP2 inhibition is associated with hematological toxicity, affecting the tolerability and efficacy of monotherapy and combination therapies. Furthermore, synthetic lethality in BRCA-mutated cancers depends mostly on PARP1, whereas PARP2 is not essential. These findings promoted the development of next-generation PARPis with greater selectivity for PARP1 than for PARP2. Summary: In this review, we discuss the next-generation PARPis that target PARP1 and show promise in terms of improved safety, tolerability, pharmacological profiles, and efficacy compared to existing clinically approved PARPis. These next-generation PARP1-selective inhibitors hold significant promises for improving the survival and outcomes of cancer patients.","journal":"Current Breast Cancer Reports","year":2025,"id":512975,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":268637,"name":"Mateusz Opyrchal","orcid":"0000-0003-2454-7441","position":1,"is_corresponding":false},{"id":386162,"name":"Alo Ray","orcid":"0000-0002-7505-1203","position":0,"is_corresponding":true}],"reference_count":127,"raw_metadata":null,"created_at":"2026-07-19T02:48:11.233009Z","pmid":"40521389","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}