Protein kinases are the second most sought-after G-protein coupled receptors as drug targets because of their overexpression, mutations, and dysregulated catalytic activities in various pathological conditions. Till 2019, 48 protein kinase inhibitors have received FDA approval for the treatment of multiple illnesses, of which the majority of them are indicated for different malignancies. One of the attractive sub-group of protein kinases that has attracted attention for drug development is the family members of MAPKs that are recognized to play significant roles in different cancers. Several inhibitors have been developed against various MAPK members; however, none of them as monotherapy has shown sustainable efficacy. One of the MAPK members, called Mixed Lineage Kinase 3 (MLK3), has attracted considerable attention due to its role in inflammation and neurodegenerative diseases; however, its role in cancer is an emerging area that needs more investigation. Recent advances have shown that MLK3 plays a role in cancer cell survival, migration, drug resistance, cell death, and tumor immunity. This review describes how MLK3 regulates different MAPK pathways, cancer cell growth and survival, apoptosis, and host's immunity. We also discuss how MLK3 inhibitors can potentially be used along with immunotherapy for different malignancies.

蛋白激酶是作为药物靶标的第二受欢迎的 G 蛋白偶联受体，因为它们在各种病理条件下的过表达、突变和失调的催化活性。至 2019 年，已有 48 种蛋白激酶抑制剂获得 FDA 批准用于治疗多种疾病，其中大部分用于不同的恶性肿瘤。引起药物开发关注的有吸引力的蛋白激酶亚组之一是 MAPKs 家族成员，这些成员被认为在不同癌症中发挥重要作用。已经针对各种 MAPK 成员开发了几种抑制剂；然而，它们都没有作为单一疗法显示出可持续的疗效。MAPK 成员之一，称为 Mixed Lineage Kinase 3 (MLK​​3)，由于其在炎症和神经退行性疾病中的作用而引起了相当大的关注；然而，它在癌症中的作用是一个需要更多研究的新兴领域。最近的进展表明，MLK3 在癌细胞存活、迁移、耐药性、细胞死亡和肿瘤免疫中发挥作用。这篇综述描述了 MLK3 如何调节不同的 MAPK 通路、癌细胞的生长和存活、细胞凋亡和宿主的免疫。我们还讨论了 MLK3 抑制剂如何与免疫疗法一起用于治疗不同的恶性肿瘤。这篇综述描述了 MLK3 如何调节不同的 MAPK 通路、癌细胞的生长和存活、细胞凋亡和宿主的免疫。我们还讨论了 MLK3 抑制剂如何与免疫疗法一起用于治疗不同的恶性肿瘤。这篇综述描述了 MLK3 如何调节不同的 MAPK 通路、癌细胞的生长和存活、细胞凋亡和宿主的免疫。我们还讨论了 MLK3 抑制剂如何与免疫疗法一起用于治疗不同的恶性肿瘤。