Targeted protein degradation has become a popular strategy to expand the druggable proteome, but therapeutic options for membrane proteins are limited. Sun et al. have now developed R-spondin chimeras (ROTACs) that effectively mediate lysosomal degradation of PD-L1, thus providing a modular platform that may be applicable to other membrane proteins.

Aberrant expression of transmembrane mucins promotes tumor progression and interferes with immunological and medicinal elimination of cancer cells. In a recent article, Pedram et al. directed an attenuated bacterial mucin-specific protease to HER2-positive tumor cells and observed decreased tumor growth rates and extended survival of mice bearing HER2-positive tumors.