Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis

Abstract

Aberrations in the Wnt signaling pathway, particularly mutations in genes like APC and β-catenin, are pivotal in initiating and driving the progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays a key role in regulating Wnt signaling by controlling the activation, modulation, and secretion of essential signaling molecules that contribute to CRC progression. This review explores the connection between membrane trafficking and Wnt signaling, with a specific focus on macropinocytosis—an endocytic process involved in nutrient uptake that also plays a role in Wnt signal regulation. The relationship between Wnt signaling and macropinocytosis, critical in both embryonic development and cancer onset, reveals a new dimension for therapeutic intervention. Targeting Wnt signaling through the modulation of macropinocytosis and broader membrane trafficking pathways presents a promising therapeutic strategy, with several candidates already in early clinical trials. These emerging approaches underscore the potential of targeting Wnt and its associated membrane trafficking processes for CRC treatment, aligning with the development of innovative therapies.