The regulatory function of mixed lineage kinase 3 in tumor and host immunity

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.