Descoberta nova abordagem para induzir a morte de células de cancro oral

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Descoberta nova abordagem para induzir a morte de células de cancro oral

Quinta, 02.01.2025

O cancro de cabeça e pescoço, incluindo o carcinoma oral de células escamosas (OSCC), é uma das formas de cancro mais comuns no mundo, que apresenta desafios significativos, como a resistência aos tratamentos tradicionais. O Cetuximab, um medicamento que bloqueia o recetor de crescimento epidérmico (EGFR), é amplamente usado, mas a sua eficácia apresenta limitações.

 

Investigadores do Instituto Universitário de Ciências da Saúde, IUCS-CESPU (UNIPRO e UCIBIO-1H-TOXRUN) investigaram a combinação do Cetuximab com moléculas que inativam proteínas essenciais para a divisão celular correta, como a MPS-1, a Aurora-B, e a KSP. A combinação resultou na morte significativa das células derivadas do cancro oral testadas. Este resultado abre caminho para testar a combinação nos ensaios clínicos, podendo vir a ser acrescentada às terapias existentes como uma das alternativas.

 

Autores e afiliações:

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.

 

Revista: Cancers

 

Link: https://www.mdpi.com/2072-6694/16/22/3732