Unraveling the impact of tumor microenvironment acidosis: From genes to mouse models

Summary: Solid tumors are heterogeneous environments, containing niches of varying hypoxia, acidosis, and nutrient deprivation. Evidence from us and others shows that such hostile conditions can endow cancer cells with highly aggressive traits, including increased growth, invasiveness, and rewired metabolism. Such niches can also support cancer stem cells and protect cancer cells against chemotherapeutic and immune-oncological therapies. Accordingly, we recently demonstrated that acid-adapted pancreatic cancer cells give rise to highly aggressive tumors with increased metastatic potential in vivo. Understanding these niches and their impact can uncover new targets for improving treatment of aggressive cancers. I will present our recent work in which we combine in vitro and in vivo cancer models, microfluidics, and spatial transcriptomics to study the mechanisms through which tumor acidosis may drive cancer aggressiveness.