Chemotherapy, which saves lives in childhood cancers, leaves a genetic “signature” on the liver, accelerating mutations in healthy cells. The discovery explains the risks in adulthood, without detracting from the effectiveness of this treatment.
Chemotherapy can save lives because it limits the proliferation of tumor cells. But the same drugs that block the progression of tumors, by acting on the ability of cells to multiply, can also damage some healthy cells that have the ability to grow very rapidly. The human body has the ability to regenerate cells and tissues and for this reason, when oncological treatments are finished, many of the side effects of chemotherapy disappear. However, chemotherapy faced in childhood can leave lasting marks on healthy tissue.
A study published in Science has now managed to identify the specific signature left by two types of chemotherapy on the healthy liver cells of children who had undergone treatments to cure pediatric tumors. The results of the study are important in explaining some health problems in adults who underwent cancer treatment during childhood.
An organ aged before its time
A group of scientists led by Anna Wenger, researcher at the Wellcome Sanger Institute in the United Kingdom, studied the effects on DNA of chemotherapy based on drugs composed of platinum salts (cisplatin and carboplatin) on the liver of young patients treated for hepatoblastoma, the most common liver cancer in children, which is generally diagnosed during the first 3 years of life.
The scientists collected liver tissue from patients who had received a liver transplant. They were thus able to analyze samples of both still healthy liver cells and tumor cells.
Through a highly sensitive genome sequencing technique, called NanoSeq, the researchers obtained sequences of single DNA molecules, and realized that the patients’ healthy tissue now resembled, in terms of number and type of accumulated mutations, the livers of adult people.
The chemotherapy-related mutations had accumulated until the organ resembled a liver aged with age. In fact, as the human body ages, the tissues accumulate mutations that the DNA repair mechanisms only partially compensate for, due both to non-modifiable factors (such as metabolism) and modifiable factors such as the habit of alcohol and smoking, the medicines taken and the environment in which one lives. Chemotherapy in childhood had reproduced the same effect in an accelerated way.
This same signature of distinctive DNA mutations was present in liver tissue that had been exposed to chemotherapy (both healthy and cancer-affected liver tissue), but not in other organs—evidence that treatment can leave long-lasting genetic damage in healthy tissue.
This high number of unwanted mutations could increase the risk of liver dysfunction, cirrhosis (the accumulation of scars and nodules in the liver) or secondary cancers in adulthood: results like the one just published will allow earlier recognition of these conditions and more timely interventions.
At the same time, recalls a commentary article published in support of the discovery, we must not forget that, before platinum-based chemotherapy, only 20-30% of children with hepatoblastoma survived the disease. These treatments have improved the rate of complete surgical removal of tumors and increased the survival of patients with localized hepatoblastoma to over 90% 5 years after diagnosis.
