A new study published in Nature explores the dynamic changes that colorectal cancer (CRC) cells undergo during their transition to the metastatic state by comparing primary tumours with metastases. “Clinically, metastases are less responsive to therapy than primary tumours in the same patients, despite harbouring the same mutations,” says Karuna Ganesh, co-corresponding author of the study.

The researchers collected trios of same-patient biopsy samples of normal colon, primary and metastatic tissue from 31 patients with microsatellite-stable mismatch-repair-proficient CRC undergoing synchronous colectomy and liver metastasectomy for metastatic CRC treatment. “We applied computational algorithms to single-cell RNA-sequencing collected from each trio to identify a series of conserved intermediate steps during the transition to the metastatic steps, including a reversion to an earlier fetal-like state along the transition,” says co-corresponding author Dana Pe’er.