Genetic testing offers hope for targeted childhood cancer therapies microbiologystudy

New research has looked into a comprehensive and structured approach to genetic testing, matching children and young people with cancer to targeted treatments. The study aimed to advance precision medicine in the UK to help young cancer patients receive more targeted cancer treatments, an important step towards increasing survival rates and reducing the side-effects of treatment.

Researchers looked at tumors of relapsed childhood cancers to see how they adapt and change in response to treatment. Researchers showed that a ctDNA blood test, a less invasive approach to track tumor evolution, can add valuable information and, in some patients, detect additional DNA mutations in the tumor that were missed by tumor biopsy. The paper is published Cancer Discovery.

The first phase of the Stratified Medicine Paediatrics (SMPaeds1) program is advancing precision medicine in the UK to help young cancer patients receive more targeted and less toxic treatments.

SMPaeds1 aimed to advance precision medicine for children and young people whose cancer has returned. The project focused on analyzing childhood cancer tumors at diagnosis and relapse stages of the cancer journey, to help better understand how the tumors evolve.

The research team from The Institute of Cancer Research, London introduced the use of ctDNA—DNA that is released into the bloodstream circulation by cancer cells—as a potential tool for tracking cancer progression and identifying new treatment targets. The ctDNA test offers a less invasive way to monitor how tumor mutations change over time and can add additional information that is complimentary to tissue biopsy.

The first phase of the precision medicine research project was completed in October 2023 and was led by, Professor Louis Chesler, Professor of Paediatric Cancer Biology at The Institute of Cancer Research, London, and Consultant in Paediatric Oncology at The Royal Marsden NHS Foundation Trust, together with author, Dr. Sally George, Group Leader of the Developmental Oncology group at the Institute of Cancer Research, London and an Honorary Consultant Paediatric Oncologist at The Royal Marsden NHS Foundation Trust.

Dr. George explains, “We showed that ctDNA analysis can add valuable information and that in some patients it can detect additional DNA mutations that are in the tumor but were missed by tumor biopsy.

“SMPaeds1 is the largest study with matched ctDNA and tissue sequencing to date and shows the value of ctDNA testing for children with cancer. We are working with colleagues across Europe to transition ctDNA analysis from being a research test to being available clinically.

“The project also identifies DNA mutations that become enriched at relapse. This will help us prioritize future research to understand why those mutations are enriched and if we can develop new treatments to target cancers with those mutations.”

The second phase of the research program, SMPaeds2, is currently underway and aims to develop and study new tests that will build upon the success of the first phase of the program. SMPaeds2 will investigate blood cancers and solid tumors in children and young people, including in the brain, muscle and bone, which can be more difficult to access, diagnose and treat.

Children with Cancer UK CEO, Amar Naher said, “We’re proud to be involved in a research project leading the way in advancing precision medicine in the UK. Children with Cancer UK’s mission is to create a world where every child and young person survives their cancer diagnosis. We strive to meet this mission through funding impactful research.

“The outcomes from the SMPaeds programs could help in the development of targeted treatments and could lead to improved, less invasive ways of monitoring and treating childhood cancers. By identifying genetic changes that drive relapse, the project helps advance personalized treatments, supporting the charity’s aims to improve survival rates and quality of life for young cancer patients.”

Dr. Laura Danielson, children’s and young people’s research lead at Cancer Research UK, said, “We’re excited about this new research from the SMPaeds program revealing the potential use of less invasive blood tests to better understand solid tumors in children and young people.

“These data demonstrating that analyzing ctDNA could lead to a more complete picture of the tumor and how it is changing over time are incredibly important. This will pave the way for a better understanding of what drives relapse or lack of response to treatment, and with it the hope of developing better, more targeted treatments. We’re proud to fund innovative research like this, which is unlocking new ways to study and potentially treat childhood cancers to give young cancer patients the best possible chance to live long, healthy lives.”