Associação Portuguesa de Investigação em Cancro
New Approach Combines EGFR and Cell Division Pathways to Boost Oral Cancer Treatment
New Approach Combines EGFR and Cell Division Pathways to Boost Oral Cancer Treatment

Authors and Affiliations:
Mafalda Calheiros-Lobo 1,†,João P. N. Silva 1,†,Leonor Delgado 1,2,Bárbara Pinto 1,3,Luís Monteiro1,4,Carlos Lopes 1, Patrícia M. A. Silva 1,5,6,* and Hassan Bousbaa 1,*
1UNIPRO—Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
2Pathology Department, INNO Serviços Especializados em Veterinária, 4710-503 Braga, Portugal
3Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Pres. Antônio Carlos, 6627, Belo Horizonte 31270-901, Brazil
4Medicine and Oral Surgery Department, University Institute of Health Sciences—CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal
5Associate Laboratory i4HB, Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
6UCIBIO—Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal
*Authors to whom correspondence should be addressed.
†These authors contributed equally to this work.
Abstract:
Background/Objectives: Head and neck cancer (HNC) is among the most common cancer types globally, with its incidence expected to increase significantly in the coming years. Oral squamous cell carcinoma (OSCC), the predominant subtype, exhibits significant heterogeneity and resistance to treatment. Current therapies, including surgery, radiation, and chemotherapy, often result in poor outcomes for advanced stages. Cetuximab, an EGFR inhibitor, is widely used but faces limitations. This study explores the combined inhibition of EGFR and mitotic proteins to enhance treatment efficacy. Methods: We analyzed the effects of co-treating OSCC cells with small molecules targeting MPS-1 (BAY1217389), Aurora-B (Barasertib), or KSP (Ispinesib), alongside Cetuximab. The rationale is based on targeting EGFR-mediated survival pathways and the mitotic checkpoint, addressing multiple cell cycle phases and reducing resistance. Results: Our findings indicate that inhibiting MPS-1, Aurora-B, or KSP enhances Cetuximab’s therapeutic potential, promoting increased cancer cell death. Additionally, we examined EGFR, MPS-1, Aurora-B, and KSP expression in OSCC patient samples, revealing their clinicopathologic significance. Conclusions: This combinatorial approach suggests a promising strategy to improve treatment outcomes in OSCC.
Journal: Cancers