The term metastasis It is one of those oncology words that has passed into the collective vocabulary. Virtually everyone knows that it refers to the spread of cancer to the rest of the body. However, many times we ignore all the mysteries that still saves this process for science.
Recently, a team of researchers from the Institute of Biomedical Research of Barcelona (IRB) led by Dr. Eduard Batlle has solved one of these mysteries by identifying residual colon cancer tumor cells hidden in the liver and lung that evolve to form metastases in these organs, as published in an article in the prestigious specialized media Nature. Not only that, but they have found that changing the way the disease is approached could reduce the risk of relapse. 20 minutes contacted one of these authors, the Dr. Adrià Cañellas-Partnersto explain these discoveries and the horizons that remain to be unraveled regarding metastasis.
Metastasis is like a waterfall
“Many things are known about metastasis, and it has been studied a lot for ten or fifteen years because it was found to be the main cause of death in patients,” explains this expert, “but we have to see that when we talk about metastasis it is a complex process, covering many stages”.
“Metastasis begins when there are cells in the tumor that break off, and then enter the circulation, they have to reach the organ, start to grow, remain in a state of latency… it’s called the metastatic cascadebecause there are many steps, many stages”, he continues.
“There is a lot of research and there will continue to be, because it is very necessary,” says the researcher. For example, they have discovered many genes involved in all these steps.”
study what is not seen
“The special thing about our article is that, while metastasis is often studied once it is already formed (because it is easier; we have samples, methods…), what we have done is develop methods to study metastasis when you don’t see“, it states.
And he develops: “This moment is what is called latency. The time from when they reach the organ until the metastases are detectable. For example, in colon cancer, we may be talking about a term of between two and three years. In breast cancer, 10 to 15 years.”
“What we’ve done is recreate a model where we implant a primary tumor in the mice and do surgery. So these mice have residual disease that over time is going to metastasize. And one thing we did notice is that the more mutations have the tumor, more grows once it reaches its destination; but there are others with fewer mutations that may take longer.”
“However, in colon cancer” adds Cañellas-Socias “what is the input or the signal that makes some dormant cells to metastasize we do not know. It is being investigated, and we believe that with models like ours, more people will be encouraged to do this type of study.”
“By analyzing the transcriptome we can know the risk that a patient has of developing metastases after surgery”
Therefore, genetic analysis (in which tumor mutations are revealed) and epigenetic (the one that studies the way and the degree in which genes are expressed) is key to determining the risk of a certain tumor and even the type of treatments that may be most useful.
“By analyzing the transcriptome” this researcher agrees (the transcriptome refers to the readings of the genes that are present in a cell, which is an epigenetic analysis) “we can predict the risk that a patient has of developing metastasis after surgery.
Changing how cancer is treated
However, it seems that this risk can be further reduced. Cañellas-Socias details it as follows: “In our experimental models, immunotherapies have the potential to prevent future development of metastases if they occur preoperatively, before removing the primary tumor. This is surprising, because these colon cancer drugs don’t work once the metastasis is already formed.”
“In other words, the residual disease can be eliminated if it is attacked in the latency stage, and this is due to changes in the tumor microenvironment” (The tumor microenvironment, he notes, is “the protective barrier that the tumor mounts using cells theoretically healthy to those that corrupt to protect themselves from the immune system”). “What happens is that, at the beginning, this protective layer is not so powerful and then the immunotherapies are capable of reactivate the immune system.
“These results,” he clarifies, “are in the phase of observing relapses in patients. But I think that in the next two years or so we will know it. And if it works, this could change how it’s treated colon cancer.”
“When colon cancer is diagnosed, instead of scheduling surgery to remove the primary tumor and then applying chemotherapy, what we would do is give preventive immunotherapy and then remove the primary tumor,” he concludes.
Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X. et al. Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells. Nature (2022). DOI: https://doi.org/10.1038/s41586-022-05402-9