Oncogenic signaling pathways associated with immune evasion and resistance to immune checkpoint inhibitors in cancer.
Semin Cancer Biol
; 65: 51-64, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-31874279
ABSTRACT
Immune checkpoint inhibitors (ICIs) are novel class of anti-cancer drugs that exhibit significant therapeutic effects even in patients with advanced-stage cancer. However, the efficacy of ICIs is limited due to resistance. Therefore, appropriate biomarkers to select patients who are likely to respond to these drugs as well as combination therapy to overcome the resistance are urgently necessary. Cancer is caused by various genetic alterations that lead to abnormalities in oncogenic signaling pathways. The aberrant oncogenic signaling pathways serve as not only prognostic and predictive biomarkers, but also targets for molecularly targeted therapy. Growing evidence shows that the aberrant oncogenic signaling pathways in cancer cells facilitate the resistance to ICIs by modulating the regulation of immune checkpoint and cancer immune surveillance. Indeed, it has been demonstrated that some molecular targeted therapies significantly improve the efficacy of ICIs in preclinical and clinical studies. In this review, we highlighted several oncogenic signaling pathways including receptor tyrosine kinases (RTKs), MAPK, PI3K-AKT-mTOR, JAK-STAT, Hippo, and Wnt pathways, and summarized the recent findings of the mechanisms underlying the regulation of cancer immunity and the ICI resistance induced by these aberrant oncogenic signaling pathways in cancer cells. Moreover, we discussed potential combination therapies with ICIs and molecularly targeted drugs to overcome the resistance and increase the efficacy of ICIs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistencia a Medicamentos Antineoplásicos
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Inibidores de Checkpoint Imunológico
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Imunoterapia
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Neoplasias
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Semin Cancer Biol
Ano de publicação:
2020
Tipo de documento:
Article