有必要识别生物标志物来预测免疫检查点抑制剂（ICI）的功效。考虑到体细胞突变衍生的新抗原会诱导强烈的免疫反应，据报道，肿瘤突变负荷高的患者倾向于对 ICI 做出反应。因此，新抗原突变的原始功能及其对肿瘤微环境（TME）的影响需要引起重视。 RNF43 是一种 RING E3 泛素连接酶，大多数癌症的长期幸存者都具有保守的 RNF43 突变模式。此外，与微卫星稳定性肿瘤患者相比，高微卫星不稳定性患者的RNF43突变率更高，后者对ICI治疗更敏感。因此，RNF43已成为多种癌症免疫治疗的有前途的生物标志物。本综述重点关注癌症中 RNF43 突变的最新知识。我们总结了涉及 RNF43 调节活动的癌症标志，并强调了其对 WNT 信号传导和肿瘤微环境极其复杂的调节。还对与 RNF43 相互作用的关键基因进行了总结和讨论。此外，我们强调并提出了针对 RNF43 和基于 RNF43 的组合与已建立的免疫疗法和联合疗法的新策略。这些努力可能为基于 RNF43 的癌症靶向治疗提供新的视角。© 2024 John Wiley

Identifying biomarkers to predict immune checkpoint inhibitor (ICI) efficacy is warranted. Considering that somatic mutation-derived neoantigens induce strong immune responses, patients with a high tumor mutational burden reportedly tend to respond to ICIs. Therefore, the original function of neoantigenic mutations and their impact on the tumor microenvironment (TME) require attention. RNF43 is a type of RING E3 ubiquitin ligase, and long-term survivors in most cancers had conserved patterns of mutations of RNF43. Also, high microsatellite instability patients had a higher RNF43 mutation rate compared with microsatellite stability tumor patients, who were more sensitive to ICI treatment. Therefore, RNF43 has become a promising biomarker of immunotherapy in a wide range of cancers. This review focuses on the up-to-date knowledge of RNF43 mutation in cancer. We summarize the cancer hallmarks involving activities regulated by RNF43 and highlight its extremely sophisticated regulation of WNT signaling and tumor microenvironment. The key genes interacting with RNF43 have also been summarized and discussed. Additionally, we highlight and propose new strategies of targeting RNF43 and RNF43-based combinations with established immunotherapy and combination therapy. These efforts may provide new perspectives for RNF43-based target therapy in cancer.© 2024 John Wiley & Sons Ltd.