1. Academic Validation
  2. Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer: A Plausible Alliance to Enhance Cell Death

Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer: A Plausible Alliance to Enhance Cell Death

  • Cancers (Basel). 2024 Nov 5;16(22):3732. doi: 10.3390/cancers16223732.
Mafalda Calheiros-Lobo 1 João P N Silva 1 Leonor Delgado 1 2 Bárbara Pinto 1 3 Luís Monteiro 1 4 Carlos Lopes 1 Patrícia M A Silva 1 5 6 Hassan Bousbaa 1
Affiliations

Affiliations

  • 1 UNIPRO-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.
  • 2 Pathology Department, INNO Serviços Especializados em Veterinária, 4710-503 Braga, Portugal.
  • 3 Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Av. Pres. Antônio Carlos, 6627, Belo Horizonte 31270-901, Brazil.
  • 4 Medicine and Oral Surgery Department, University Institute of Health Sciences-CESPU (IUCS-CESPU), 4585-116 Gandra, Portugal.
  • 5 Associate Laboratory i4HB, Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal.
  • 6 UCIBIO-Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal.
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.

Keywords

KSP inhibitor; MPS-1 inhibitor; antimitotics; antitumor activity; aurora-B inhibitor; cetuximab; combination treatment; oral cancer.

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