Resumen
Kirsten rat sarcoma virus (KRAS)-mutant cancers are frequent, metastatic, lethal, and largely undruggable. The aim of this study was to investigate the pathways through which KRAS-mutant cancers foster their growth, thereby unravelling novel therapeutic targets. We show that KRAS-mutant tumors secrete the protein versican, which then drives the activation of NF-?B kinase (IKK) ß in a type of host immune cells called macrophages. Following this activation, macrophages fuel the tumor with interleukin (IL)-1ß, to close an inflammatory loop through which KRAS-mutant cancers attract host immune cells to the tumor site to accelerate tumor growth and aggressiveness. Importantly, we show that targeting IL-1ß and/or versican can be an effective treatment for KRAS-mutant cancers, holding great promise for cancer patients.