Targeting stem cell marker LGR5 in colorectal cancer
Leucine-rich repeat-containing G protein-coupled receptor 5 marks highly plastic colorectal cancer stemlike cells with roles in tumor initiation, progression, and metastasis.
LGR5 potentiates Wnt/β-catenin and adhesion signaling through mechanisms that may be independent of RNF43/ ZNRF3 E3 ligases.
Dynamic shifts between LGR5+ and LGR5− cancer cell states mediate resistance to chemotherapies and epidermal growth factor receptor/kirsten rat sarcoma viral oncogene homolog/mitogen activated protein kinase (EGFR/KRAS/ MAPK) pathway inhibitors in colorectal cancer.
Several LGR5-directed therapies are being developed as promising cancer treatments, with current approaches including peptibody– and antibody– drug conjugates, chimeric antigen receptor T cells, bispecific antibodies, and combination therapies, all highlighting LGR5 as a key therapeutic target for various cancer types.
https://www.cell.com/trends/cancer/fulltext/S2405-8033(26)00037-3
