Throughout our lives the cells of the body change , that is, they undergo genetic alterations. But don’t panic: in most cases these changes are harmless, because they respond to a programmed mechanism of cell multiplication and cell death, which happens in an orderly manner. However, genetic alterations can occur that cause cells to ignore these orders and begin to multiply in an aberrant way, resulting in cancer. Tumors can occur as a result of alterations in the epigenome, caused by internal factors, due to an error in DNA processing; or external, such as solar radiation, tobacco smoke, or some toxic substances.
Now, a team of researchers from the Institute for Biomedical Research (IRB Barcelona) led by ICREA researcher Núria López-Bigas, head of the Biomedical Genomics Laboratory and associate professor at Pompeu Fabra University, have determined for the first time the genetic alterations that cause six therapies used in the treatment of cancer : five chemotherapy and one radiotherapy.
Chemo works by damaging the DNA of cancer cells in order to kill them. The downside is that it can also overwhelm healthy cells. All in all, this treatment has managed to survive a significant portion of cancer patients. In this sense, Oriol Pich, predoctoral student at IRB Barcelona and first author of the article that has been published in Nature Genetics , is forceful: “It is important to note that chemotherapies are very effective in treating cancer .” “However, long-term side effects have also been reported in some patients. Studying the mutations produced by chemotherapies in the DNA of patients’ cells is a first step in understanding the relationship of these mutations with the long-term side effects of these therapies ”.
To carry out the study, the researchers obtained from the Hartwig Medical Foundation in the Netherlands the sequence of the metastatic tumor genomes of more than 3,500 patients, as well as information on the treatments they received. Using bioinformatic methods, they were able to identify a specific pattern in the mutations of the patients’ cells for each of the most common cancer treatments, that is, a “mutational fingerprint” of the therapies.
“Once this’ fingerprint ‘has been identified, we can quantify the mutations produced by each chemotherapy in the patients’ DNA, as well as those produced by combinations of treatments,” explains López-Bigas. “We have compared this measure with genetic alterations due to natural endogenous processes of cells. We have calculated that during the treatment period some of these chemotherapies cause DNA alterations at a rate between one hundred and one thousand times faster than we would expect in a cell ”.
The aim of the study is to improve the treatments used today to fight cancer. López-Bigas sets the goal of harnessing the potential of chemo to destroy tumor cells while minimizing the amount of mutations induced in healthy cells . “This would be achieved through a balanced combination of dose and duration of treatment,” he says.
The study has been funded by the European Research Council, the Ministry of Science, Innovation and Universities and the Department of Business and Connection of Catalonia. Oriol Pich has a grant from the Barcelona Institute of Science and Technology (BIST).
Fuente: Oriol Pich, Ferran Muiños, Martijn Paul Lolkema, Neeltje Steeghs, Abel Gonzalez-Perez and Nuria Lopez-Bigas. The mutational footprints of cancer therapies. Nature Genetics (2019). DOI: s41588-019-0525-5.
