{"doi":"10.3390/molecules29225334","title":"Palbociclib as an Antitumor Drug: A License to Kill","abstract":"<jats:p>Neoplastic cells are characterized by uncontrolled cell divisions caused by cell cycle dysregulation. Key regulatory proteins governing the transition from the G1 to the S phase are the CDK4 and CDK6 kinases, which are controlled by D-type cyclins. The CDK4/6 kinases enable the use of these proteins as targets for anticancer therapy because they prevent the growth and the development of malignant cells by inhibiting their activity. This paper surveys the clinical trial results concerning palbociclib, the first in-class FDA-approved anticancer drug for hormone-dependent breast cancer. It discusses the therapeutic applications in breast cancer as well as in solid tumors and hematopoietic malignancies. Additionally, the paper presents an analysis of palbociclib resistance acquired during therapy and explores new approaches, such as modifications to palbociclib that enhance its desired activity or open up new therapeutic possibilities (PROTACs).</jats:p>","journal":"Molecules","year":2024,"id":628762,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1628085,"name":"Federica Cossu","orcid":"0000-0001-9753-3572","position":1,"is_corresponding":false},{"id":1628087,"name":"Marcin Sieńczyk","orcid":"0000-0002-5528-5264","position":2,"is_corresponding":false},{"id":1628083,"name":"Agnieszka Łupicka-Słowik","orcid":"0000-0002-5593-5167","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Palbociclib as an Antitumor Drug: A License to Kill","abstract":"<jats:p>Neoplastic cells are characterized by uncontrolled cell divisions caused by cell cycle dysregulation. Key regulatory proteins governing the transition from the G1 to the S phase are the CDK4 and CDK6 kinases, which are controlled by D-type cyclins. The CDK4/6 kinases enable the use of these proteins as targets for anticancer therapy because they prevent the growth and the development of malignant cells by inhibiting their activity. This paper surveys the clinical trial results concerning palbociclib, the first in-class FDA-approved anticancer drug for hormone-dependent breast cancer. It discusses the therapeutic applications in breast cancer as well as in solid tumors and hematopoietic malignancies. Additionally, the paper presents an analysis of palbociclib resistance acquired during therapy and explores new approaches, such as modifications to palbociclib that enhance its desired activity or open up new therapeutic possibilities (PROTACs).</jats:p>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39598723","pmcid":"PMC11596203","openalex_id":"https://openalex.org/W4404332877","authors":[],"funders":[{"funder_name":"Wroclaw University of Technology","grant_id":"8211104160","title":null}],"total_grants":1,"fwci":0.2828,"citation_percentile":0.60889289,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1420-3049/29/22/5334/pdf?version=1731480522","host_type":"journal"},{"url":"https://www.mdpi.com/1420-3049/29/22/5334/pdf?version=1731480522","host_type":"publisher"},{"url":"https://www.mdpi.com/1420-3049/29/22/5334/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/molecules29225334","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39598723","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11596203","host_type":"repository"},{"url":"https://doaj.org/article/6adb2913dd944bfb95d58ebd41a49b2d","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11596203/pdf/molecules-29-05334.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11596203","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11596203?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Advanced Breast Cancer Therapies","Protein Degradation and Inhibitors","Chronic Lymphocytic Leukemia Research"],"mesh_terms":["Antineoplastic Agents","Breast Neoplasms","Clinical Trials as Topic","Female","Humans","Piperazines","Pyridines","Drug Resistance, Neoplasm","Protein Kinase Inhibitors","Cyclin-Dependent Kinase 4","Cyclin-Dependent Kinase 6"],"keywords":["Palbociclib","Cyclin-dependent kinase 6","Kinase","Cancer","Cell cycle","Cancer research","Breast cancer","Medicine","Pharmacology","Cyclin-dependent kinase","Biology","Internal medicine","Metastatic breast cancer","Cell biology","Antitumor","Cyclin-dependent kinases","Targeted Therapy","Protac","Tnbc","Snipers"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"uniprot"},{"name":"nct"},{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T14:56:49.802574Z","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":[]}