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Papel do eixo de sinalização PD-1/PD-L1 na oncogênese e seu direcionamento por compostos naturais bioativos para imunoterapia do câncer

  • role： First author第一作者
  • Affiliation：

    Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India

Yogesh Godiyal1,  
  • Affiliation：

    Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India

Drishti Maheshwari1,  
  • Affiliation：

    Department of Experimental Embryology, Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Jastrzebiec,05-552 Magdalenka, Poland

    African Genome Center, Mohammed VI Polytechnic University, Hay Moulay Rachid, 43150 Ben Guerir, Morocco

Hiroaki Taniguchi23,  
  • Affiliation：

    Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA

Shweta S. Zinzuwadia4,  
  • Affiliation：

    Clinical Investigation and Biomedical Research Directions, Center for Genetic Engineering and Biotechnology, 11600 Havana, Cuba

Yanelys Morera-Díaz5,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India

  • Email：devesh.tewari@dpsru.edu.in
  • Introduction：* Devesh Tewari devesh.tewari@dpsru.edu.in; dtewari3@gmail.com
Devesh Tewari1*,  
  • role： Corresponding author通信作者
  • Affiliation：

    Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA

  • Email：abishayee@lecom.edu
  • Introduction：Anupam Bishayee abishayee@lecom.edu; abishayee@gmail.com
Anupam Bishayee4*

Resumo

O câncer é um problema global de saúde e uma das principais causas de mortalidade. Os inibidores de pontos de verificação imunológicos revolucionaram o campo da oncologia, emergindo como uma estratégia terapêutica poderosa. Uma via chave que tem recebido considerável atenção é o eixo de sinalização da morte celular programada-1 (PD-1)/ligante da morte celular programada-1 (PD-L1). A interação entre o PD-L1 expresso em células tumorais e o PD-1 reduz a resposta imune inata e, assim, compromete a capacidade do sistema imunológico do corpo. Além disso, controla o fenótipo e a funcionalidade dos componentes imunológicos inatos e adaptativos. Uma série de anticorpos monoclonais, incluindo avelumabe, atezolizumabe, camrelizumabe, dostarlimabe, durvalumabe, sinitilimabe, toripalimabe e zimberelimabe, foram desenvolvidos para direcionar a interação entre PD-1 e PD-L1. Esses agentes podem induzir um amplo espectro de complicações autoimunes semelhantes que podem afetar qualquer sistema orgânico. Estudos recentes têm se concentrado no efeito de vários compostos naturais que inibem os pontos de verificação imunológicos. Isso pode contribuir para o arsenal existente de medicamentos anticâncer. Vários agentes naturais bioativos têm demonstrado afetar o eixo de sinalização PD-1/PD-L1, promovendo a apoptose das células tumorais, influenciando a proliferação celular e, eventualmente, levando à morte das células tumorais e inibindo a progressão do câncer. No entanto, existe uma lacuna substancial no conhecimento sobre o papel de diferentes compostos naturais que visam PD-1 no contexto do câncer. Portanto, esta revisão visa fornecer uma conexão comum entre o bloqueio de PD-1/PD-L1 e os efeitos anticâncer de moléculas naturais distintas. Além disso, o foco principal estará no mecanismo subjacente de ação, bem como na eficácia clínica das moléculas bioativas. Desafios atuais, juntamente com o escopo das futuras direções de pesquisa visando as interações PD-1/PD-L1 através de substâncias naturais, também são discutidos.

Palavras-chave

Câncer;PD-1/PD-L1;Interações;Compostos naturais;Alvos terapêuticos

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