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.

免疫检查点抑制剂（ICIs）是一类新型的抗癌药物，即使在晚期癌症患者中也显示出显着的治疗效果。但是，ICI的疗效由于耐药性而受到限制。因此，迫切需要合适的生物标志物来选择可能对这些药物有反应的患者，以及克服耐药性的联合疗法。癌症是由导致致癌信号通路异常的各种遗传改变引起的。异常的致癌信号通路不仅可以作为预后和预测性生物标志物，而且还可以作为分子靶向治疗的靶标。越来越多的证据表明，癌细胞中异常的致癌信号通路通过调节免疫检查点和癌症免疫监视的调控，促进了对ICI的抵抗。实际上，已经证明某些分子靶向疗法在临床前和临床研究中显着提高了ICI的疗效。在这篇综述中，我们重点介绍了几种致癌信号通路，包括受体酪氨酸激酶（RTKs），MAPK，PI3K-AKT-mTOR，JAK-STAT，河马和Wnt通路，并概述了调节癌症免疫力的机制的最新发现。这些异常的致癌信号通路在癌细胞中诱导的ICI抗性。此外，我们讨论了与ICI和分子靶向药物的潜在组合疗法，以克服ICI的耐药性并提高ICI的疗效。我们重点介绍了几种致癌信号通路，包括受体酪氨酸激酶（RTKs），MAPK，PI3K-AKT-mTOR，JAK-STAT，河马和Wnt通路，并概述了调节癌症免疫力和ICI耐药性的机制的最新发现这些异常的致癌信号通路在癌细胞中被诱导。此外，我们讨论了与ICI和分子靶向药物的潜在组合疗法，以克服ICI的耐药性并提高ICI的疗效。我们重点介绍了几种致癌信号通路，包括受体酪氨酸激酶（RTKs），MAPK，PI3K-AKT-mTOR，JAK-STAT，河马和Wnt通路，并概述了调节癌症免疫力和ICI耐药性的机制的最新发现这些异常的致癌信号通路在癌细胞中被诱导。此外，我们讨论了与ICI和分子靶向药物的潜在组合疗法，以克服ICI的耐药性并提高ICI的疗效。