Therapeutics: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5; GPR49)

Mouse studies suggest anti-LGR5 antibody-drug conjugates (ADCs) could help treat colorectal cancer. The ADCs consisted of an antibody against the cancer stem cell marker LGR5 conjugated to the antimitotic agent monomethyl auristatin E (MMAE) or a metabolite of the anthracycline antibiotic nemorubicin. In two xenograft mouse models of LGR5-positive colon cancer, each ADC decreased tumor growth compared with the anti-LGR5 antibody alone or ADCs based on an isotype control antibody. In a third mouse model of LGR5-positive colon cancer, the anti-LGR5-MMAE ADC decreased tumor growth and increased survival compared with the control ADC or vehicle. Next steps include further exploring ways to enhance the efficacy of ADCs conjugated to targeted anticancer drugs. ...