{"doi":"10.1101/2021.06.16.448722","title":"Tumor suppressor PLK2 may serve as a biomarker in triple-negative breast cancer for improved response to PLK1 therapeutics","abstract":"Abstract Polo-like kinase (PLK) family members play important roles in cell cycle regulation. The founding member PLK1 is oncogenic and preclinically validated as a cancer therapeutic target. Paradoxically, PLK2 (chromosome 5q11.2) is frequently deleted in human breast cancers, preferentially in basal-like and triple-negative breast cancer subtypes. Here, we found that PLK2 was tumor suppressive in breast cancer and knockdown of PLK1 rescued phenotypes induced by PLK2-loss both in vitro and in vivo . We also demonstrated that PLK2 directly interacted with PLK1 at prometaphase and that mutations in the kinase domain of PLK2, but not polo-box binding domains, changed their interaction pattern. Furthermore, treatment of syngeneic transplantation mouse tumor models and patient-derived xenografts using the PLK1 inhibitor volasertib alone, or in combination with carboplatin, indicated that PLK2-low breast tumors had a significantly better response to these drugs. Re-expression of PLK2 in an inducible PLK2-null mouse model reduced the therapeutic efficacy of volasertib. Taken together, our data suggest PLK2 loss may serve as a biomarker to predict response to PLK1 therapeutics, alone and in combination with chemotherapy. Significance The tumor suppressive role of PLK2, and its relationship with the oncogene PLK1, provide a mechanistic rationalization to use PLK1 inhibitors in combination with chemotherapy to treat PLK2 low/deleted tumors. TNBC, and other cancers with low PLK2 expression, are such candidates to leverage precision medicine to identify patients who might benefit from treatment with these inhibitors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225032,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":827522,"name":"Elena B. Kabotyanski","orcid":null,"position":1,"is_corresponding":false},{"id":827523,"name":"Elizabeth Villegas","orcid":null,"position":2,"is_corresponding":false},{"id":827210,"name":"Jonathan H. Shepherd","orcid":"0000-0001-6322-6347","position":3,"is_corresponding":false},{"id":827524,"name":"Deanna Acosta","orcid":null,"position":4,"is_corresponding":false},{"id":639393,"name":"Clark Hamor","orcid":null,"position":5,"is_corresponding":false},{"id":766905,"name":"Tingting Sun","orcid":"0000-0003-3298-3075","position":6,"is_corresponding":false},{"id":827525,"name":"Celina Montmeyor-Garcia","orcid":null,"position":7,"is_corresponding":false},{"id":546801,"name":"Xiaping He","orcid":"0000-0001-9464-7910","position":8,"is_corresponding":false},{"id":379377,"name":"Lacey E. Dobrolecki","orcid":"0000-0001-6839-629X","position":9,"is_corresponding":false},{"id":225696,"name":"Thomas F. Westbrook","orcid":"0009-0006-9711-5710","position":10,"is_corresponding":false},{"id":30176,"name":"Michael T. Lewis","orcid":"0000-0002-6330-4007","position":11,"is_corresponding":false},{"id":44715,"name":"Susan G. Hilsenbeck","orcid":"0000-0002-7962-673X","position":12,"is_corresponding":false},{"id":239995,"name":"Xiang H.-F. Zhang","orcid":"0000-0002-5674-8670","position":13,"is_corresponding":false},{"id":1883,"name":"Charles M. Perou","orcid":"0000-0001-9827-2247","position":14,"is_corresponding":false},{"id":267159,"name":"Jeffrey M. Rosen","orcid":"0000-0002-6637-844X","position":15,"is_corresponding":false},{"id":621377,"name":"Yang Gao","orcid":"0000-0003-1832-4380","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-18T23:54:22.889584Z","pmid":null,"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":[]}