Targeting the EGFR/RAS/RAF signaling pathway in anticancer research: a recent update on inhibitor design and clinical trials (2020-2023).
Expert Opin Ther Pat
; 34(1-2): 51-69, 2024.
Article
em En
| MEDLINE
| ID: mdl-38450537
ABSTRACT
INTRODUCTION:
Recent years have seen significant strides in drug developmenttargeting the EGFR/RAS/RAF signaling pathway which is critical forcell growth and proliferation. Protein-protein interaction networksamong EGFR, RAS, and RAF proteins offer insights for drug discovery. This review discusses the drug design and development efforts ofinhibitors targeting these proteins over the past 3 years, detailingtheir structures, selectivity, efficacy, and combination therapy.Strategies to combat drug resistance and minimize toxicities areexplored, along with future research directions. AREA COVERED This review encompasses clinical trials and patents on EGFR, KRAS,and BRAF inhibitors from 2020 to 2023, including advancements indesign and synthesis of proteolysis targeting chimeras (PROTACs) forprotein degradation. EXPERT OPINION To tackle drug resistance, designing allosteric fourth-generationEGFR inhibitors is vital. Covalent, allosteric, or combinationaltherapies, along with PROTAC degraders, are key methods to addressresistance and toxicity in KRAS and BRAF inhibitors.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
/
Proteínas Proto-Oncogênicas B-raf
Limite:
Humans
Idioma:
En
Revista:
Expert Opin Ther Pat
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Jordânia