Plasticity in Cancer Resistance

Published in Cancer Discovery, a study led by Dr. Eduard Batlle, Dr. Carme Cortina, and Dr. Marc Martí-Renom (CNAG-CRG) has revealed that metastatic colorectal cancers resist KRAS-targeted therapies by dynamically shifting between different cellular states under treatment pressure. The researchers have shown that tumour cells exhibit strong transcriptional plasticity, enabling them to adapt under treatment pressure and evade inhibition of oncogenic KRAS signalling.

The work has established that when KRAS activity is blocked, cancer cells transition into a stem-like LGR5⁺ state that depends less on KRAS, providing an alternative survival route. These findings highlight cellular plasticity—not new mutations—as the key mechanism of resistance and show that combining KRAS inhibition with strategies targeting these emergent cell states produces more durable therapeutic responses.

More information: Study reveals why some colorectal cancers withstand pharmacological inhibition of KRAS oncogene activity