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Eduard Batlle (Foto: IRB Barcelona).

Scientists unravel the key to colon cancer relapse after chemotherapy

Scientists at IRB Barcelona, based in the Barcelona Science Park, led by Dr. Eduard Batlle have identified a cell population responsible for the recurrence of colorectal cancer after chemotherapy. The researchers have discovered the mechanism through which a small number of tumour cells resistant to chemotherapy adopt a state of lethargy or inactivity to then regenerate the tumour sometime later.  The study has been published in the scientific journal Nature Cancer.

Approximately 1 in 25 people will develop colon cancer during their lifetime and nearly 2 million cases new cases are diagnosed worldwide each year. Chemotherapy is commonly used to treat colon cancer. While this treatment is initially effective in most cases, many patients relapse after treatment.

Led by Dr. Eduard Batlle, ICREA researcher and head of the Colorectal Cancer Laboratory at IRB Barcelona, this study reveals that some tumour cells remain in a latent state and, after chemotherapy, they are reactivated, thus causing relapse.

In short, scientists have discovered that tumour stem cells with Mex3a protein activity remain in a state of latency that confers resistance to chemotherapy. Due to the action of the drugs used in this treatment, these cells adopt a state similar to the embryonic one, and sometime after chemotherapy, when the environment is more favourable, they are reactivated to regenerate the tumour in all its complexity. These persistent cells are responsible for cancer relapse after treatment.

“Chemotherapy is effective and kills most of the tumour cells but not all of them. Our discovery reveals the identity of a group of persistent cells that are resistant to chemotherapy go on to regenerate the tumour after treatment. Our work paves the way for the development of drugs to eliminate these cells, which would make chemotherapy more effective and improve survival rates,” explains Dr. Batlle, also a group leader in the Cancer CIBER (CIBERONC).

Source: IRB Barcelona.

This study has been carried out using mainly organoids, which are samples of tumours from patients (or from mouse models of advanced cancer) that can be grown in the laboratory and that reproduce the complexity of the tumour in terms of its three-dimensional structure and variability of cell types. “The organoids have allowed us to trace the evolution of the cells responsible throughout the process and observe their reaction to chemotherapy,” explains Adrián Álvarez-Varela, the first author of the study.

» Reference article: Álvarez-Varela, A., Novellasdemunt, L., Barriga, F.M. et al. Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy. Nat Cancer (2022). DOI: 10.1038/s43018-022-00402-0

» For further information: IRB Barcelona website [+]