A new study has found that chemotherapy in childhood can leave lasting genetic scars on the healthy tissues of kids treated for cancer with certain platinum-based chemo drugs. These genetic changes effectively \u201cage\u201d the affected organs by the equivalent of many years, making new diseases, and especially new cancers, that much more likely. The findings – which have been published in Science – could help explain some of the long-term health problems that children who survive cancer face later in life. Foad Rouhani, at King\u2019s College Hospital and the Francis Crick Institute, was one of the senior authors on the study. He’s been speaking with Chris Smith…<\/p>\n
Foad – We’ve known for a long time through clinical experience that children who’ve had previous cancers who then go on and survive can have medical problems further down the line many years later, secondary cancers, for example, that arise, or diseases related to the liver. And so the question we’re really trying to ask with this work was, can we somehow understand what happens at the time of their initial treatment, which may in some way explain what then happens years down the line?<\/p>\n
Chris – Are you sort of saying that the treatment itself carries a risk?<\/p>\n
Foad – Yes, we’ve known for a long time that chemotherapy, which is the backbone of many treatments for a range of cancers, we already know that chemotherapy causes a level of damage to background healthy tissues around the body, but we didn’t really have an idea of quite how extensive this damage was up until now.<\/p>\n
Chris – What’s the mechanism of that damage? Is it that it’s just flogging lots of cells and making them grow very fast to repair damage that we’re doing with the chemotherapy, or is it actually damaging the cells genetically like it is the cancer?<\/p>\n
Foad – With this work specifically, we were focusing on the liver and the way that the chemotherapy that we focused on platinum containing chemotherapy works is exactly that. It damages DNA and that’s really how it’s effective against cancers. But what we’ve shown with this paper and what we sought to clarify with our work was whether the type of damage that we were seeing in the background tissue was exactly the same genetic changes that the chemotherapy is good at against the cancer.<\/p>\n
Chris – How have you done it?<\/p>\n
Foad – We had an experimental design where we took liver tissue from children who had a rare type of liver cancer called a hepatoblastoma, and we were taking lots of different biopsies and little samples of the liver of a number of children and then applying some quite sensitive DNA sequencing technologies to this.<\/p>\n
Chris – What are you doing? Comparing the genetic sequence of the liver tissue before and after the treatment for the cancer?<\/p>\n
Foad – In a lot of these cases, we only have the sequence of the DNA once the tissue comes out. But what we’re comparing this to was, for example, other tissues such as blood from the same patient, from the same child.<\/p>\n
Chris – And what you’re asking, have we caused any new damage to the DNA in these individuals in the course of trying to treat their cancer?<\/p>\n
Foad – Exactly, exactly. So one of the techniques that we apply in these sort of scenarios is to try and detect patterns of changes within DNA mutations, the change of the DNA and mutational signatures of these patterns. We know from other work that lots of people have done that certain types of damage, such as due to tobacco from smoking or ultraviolet light, causes characteristic patterns of mutation. It’s not totally random. So the changes in the DNA are characteristic. And hence, by looking at the DNA and the changes, we can then link to a potential cause. And so what we were looking at with the tissue that we were taking was to see whether we could see a pattern which was consistent with the platinum chemotherapy that the children had been treated with. The field already knew of signatures or these patterns of DNA changes associated with platinum. So we not only saw those, but the interesting thing was we saw a completely different type of signature, which was only present in the children who had been exposed to platinum chemotherapy for one. And secondly, the new signature that we’d found associated with platinum was only seen in liver cells and not in other tissues.<\/p>\n
Chris – And what are the implications of that then? Have we effectively artificially aged these individuals in the sense that what we’ve done is add damage that is like a notch further towards a disease in waiting in these individuals?<\/p>\n
Foad – Yes, we know from lots of other work that DNA damage or mutations are associated with age and they arise over time. And so what we were able to do in this study was to compare the amount of mutations or DNA changes in the livers of these children and compare that to adults. And to our surprise, we saw that the ones who’d had a chemotherapy, the damage had actually aged the livers of the children to approximately the same as that of an adult.<\/p>\n
Chris – Does this happen in adults as well then? So if we use the same drugs in, say, ovarian cancer cases or something, do those people succumb to the same accelerated ageing? So an adult ends up with a liver of a really elderly person?<\/p>\n
Foad – It’s a very good question. That wasn’t something we looked at in this study, but I think it does follow that agents which can damage DNA, such as chemotherapy, would do this in an adult as well as a child.<\/p>\n
Chris – And what are the implications of that then? Now you’ve found that in the liver and shown that these children appear to have much older livers than they would have based on their chronological age. What does that mean for them?<\/p>\n
Foad – What we’ve really uncovered with this work is something which was there all along, but was invisible before some of the latest sort of sequencing technologies. And so really our work has highlighted that these patients do need continued follow-up. There may also be opportunities to perhaps design different types of chemotherapies for these sorts of patients.<\/p>\n","protected":false},"excerpt":{"rendered":"A new study has found that chemotherapy in childhood can leave lasting genetic scars on the healthy tissues…\n","protected":false},"author":2,"featured_media":896787,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[64,63,80196,16780,465732,33426,465733,137],"class_list":["post-896786","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-au","tag-australia","tag-cancer-risk","tag-chemotherapy","tag-childhood-chemotherapy","tag-childrens-health","tag-genetic-scars","tag-health"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/896786","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/comments?post=896786"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/896786\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media\/896787"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media?parent=896786"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/categories?post=896786"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/tags?post=896786"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}