Cancers progress and continuously adapt, making them challenging to treat. As cancer cells replicate and evolve, distinct cellular lineages, or subclones, compete to dominate and drive tumor progression. Researchers led by I-Lin Ho, Ph.D., and Andrea Viale, M.D., developed a new model for pancreatic cancer to study subclone evolution within tumors and metastases. They found that subclones undergo continuous fluctuations in representation during tumor growth, even without any external treatment, with dominant subclones suddenly collapsing and being replaced by others.
Most of these lineages were found in distant organs, even in tumors that did not metastasize. This suggests tumor dissemination is a nonspecific, widespread behavior of tumor cells and challenges the current metastatic cascade model. The results show that the fitness of a subclone within the primary lesion determines whether it disseminates and initiates a tumor at a secondary site. The researchers identified a specific molecular signature for a subset of cells within the tumor capable of sustaining tumor metastases, which could be a potential tool for patient risk stratification.