IL31RA and cancer: For example, despite a unique target (NAE, IC50 ~5 nM), MLN toxicity in various cell lines varied over three orders of magnitude showing that CRL suppression does not necessarily lead to cell death.3 Notably, recent studies have shown that CRL inhibition by MLN induces autophagy that protects cancer cells from apoptosis; moreover, blocking autophagy markedly enhanced drug efficacy.16, 17 Therefore, analysis of all possible effects of CRL inhibition is of clinical importance as it may lead to improved drug efficacy.