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They can be classified into mitotic blockers, causing SAC-induced mitotic arrest, or mitotic drivers, pushing cells through aberrant mitosis by overriding SAC. These drugs, although advancing to clinical trials, exhibit unsatisfactory cancer treatment outcomes as monotherapy, probably due to variable cell fate responses driven by cyclin B degradation and apoptosis signal accumulation networks. We investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic navitoclax in lung cancer cells treated with the selective CENPE inhibitor GSK923295 (mitotic blocker) or the MPS1 inhibitor BAY1217389 (mitotic driver). Our aim was to steer treated cancer cells towards cell death. BH3-mimetics, in combination with both mitotic blockers and drivers, induced substantial cell death, mainly through apoptosis, in 2D and 3D cultures. Crucially, these synergistic concentrations were less toxic to non-tumor cells. This highlights the significance of combining BH3-mimetics with antimitotics, either blockers or drivers, which have reached the clinical trial phase, to enhance their effectiveness.<\/jats:p>","DOI":"10.3390\/pharmaceutics16010056","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T09:15:11Z","timestamp":1703841311000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Maximizing Anticancer Response with MPS1 and CENPE Inhibition Alongside Apoptosis Induction"],"prefix":"10.3390","volume":"16","author":[{"given":"B\u00e1rbara","family":"Pinto","sequence":"first","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"},{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Pres. Ant\u00f4nio Carlos, 6627, Belo Horizonte 31270-901, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-4286","authenticated-orcid":false,"given":"Jo\u00e3o P. N.","family":"Silva","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-7321","authenticated-orcid":false,"given":"Patr\u00edcia M. A.","family":"Silva","sequence":"additional","affiliation":[{"name":"UNIPRO\u2014Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"},{"name":"1H-TOXRUN\u2014One Health Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-6011","authenticated-orcid":false,"given":"Daniel Jos\u00e9","family":"Barbosa","sequence":"additional","affiliation":[{"name":"1H-TOXRUN\u2014One Health Toxicology Research Unit, University Institute of Health Sciences, CESPU, CRL, 4585-116 Gandra, Portugal"},{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-7553","authenticated-orcid":false,"given":"Bruno","family":"Sarmento","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Institute of Biomedical Engineering, University of Porto, Rua Alfredo Allen 208, 4200-393 Porto, Portugal"}]},{"given":"Juliana Carvalho","family":"Tavares","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. 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