Furin-like enzyme dependency in KRAS-mutant colorectal cancer as a target for personalized treatment strategies.

Increasing efforts have focused on identifying vulnerabilities within the signaling networks of KRAS that sustain its oncogenic activity. Recently, Furin-like enzymes or proprotein convertase, proteases responsible for the activation of various signaling molecules, have emerged as key regulators. Furin, modulate KRAS-related signaling by processing growth factors, cytokines, and receptor tyrosine kinases (RTKs). Repression of Furin selectively impairs the proliferation and survival of KRAS-mutant colorectal cancer cells compared with wild-type KRAS cells.

Furin inhibition disrupts various RTK maturation, attenuates downstream signaling, and remodels the tumour microenvironment toward an immune-stimulatory phenotype. Furin inhibition also repress KRAS-mutant-mediated resistance by blocking the maturation of multiple escape pathways, including compensatory RTK activation. This review summarizes current evidence on the crosstalk between KRAS signaling and Furin-like enzymes, emphasizing their cooperative roles in tumour progression and immune escape. Targeting protein maturation by these enzymes may therefore represent a therapeutic approach for KRAS-mutant colorectal cancer, offering new opportunities for personalized treatment.