Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy

Version 1 : Received: 23 April 2024 / Approved: 24 April 2024 / Online: 24 April 2024 (11:35:50 CEST)

How to cite: Sriramulu, S.; Thoidingjam, S.; Siddiqui, F.; Brown, S.L.; Movsas, B.; Walker, E.; Nyati, S. BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy. Preprints 2024, 2024041612. https://doi.org/10.20944/preprints202404.1612.v1 Sriramulu, S.; Thoidingjam, S.; Siddiqui, F.; Brown, S.L.; Movsas, B.; Walker, E.; Nyati, S. BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy. Preprints 2024, 2024041612. https://doi.org/10.20944/preprints202404.1612.v1

Abstract

BUB1 is overexpressed in most human solid cancers including breast cancer. Higher BUB1 levels are associated with poor prognosis especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC. Our previous studies demonstrated that BUB1 kinase inhibitor (BAY1816032) reduced tumor cell proliferation and significantly enhanced radiotherapy efficacy in TNBC. In this study, we evaluated the effectiveness of BAY1816032 with a PARP inhibitor (olaparib), platinum agent (cisplatin), and microtubule poison (paclitaxel) alone or in combination with radiotherapy using cytotoxicity and clonogenic survival assays. BUB1 inhibitor sensitized BRCA1/2 wild-type SUM159 and MDA-MB-231 cells to olaparib, cisplatin and paclitaxel synergistically (combination index; CI

Keywords

TNBC; BAY1816032; BUB1; PARP; olaparib; cisplatin; paclitaxel; radiation; chemoradiation

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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