Oncogenic signaling pathways associated with immune evasion and the resistance to immune checkpoint inhibitors in cancer

Publication date: Available online 23 December 2019Source: Seminars in Cancer BiologyAuthor(s): Yoshie Kobayashi, Seung-Oe Lim, Hirohito YamaguchiAbstractImmune 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), RAS-RAF-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 sig...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research