Survivorship Science: Using Genomics to Predict Late Effects in Childhood Cancer

Advances in medicine mean more kids than ever beat cancer, but that’s just the beginning. Many childhood cancer survivors face long-term health challenges caused by the very treatments that saved them. This is where genomics is making a significant difference.

Understanding Late Effects in Childhood Cancer Survivors

Surviving childhood cancer is a life-changing experience, but for many, it comes with long-term health consequences. The intense treatments used to fight cancer — chemotherapy, radiation, and surgery — can leave lasting effects, sometimes appearing months or even years later. These late effects can impact almost every system in the body, affecting physical health, cognitive function, and emotional well-being.¹

One of the most common concerns is damage to the heart and lungs.¹ Certain chemotherapy drugs and radiation to the chest can weaken the heart muscle, increasing the risk of heart disease, high blood pressure, and irregular heartbeats.

Lung problems such as reduced lung capacity and scarring can make breathing more difficult, especially during physical activity. Survivors who received radiation to the chest may also have an increased risk of developing secondary cancers later in life.

Cognitive and learning difficulties are another potential late effect, particularly for kids who received radiation to the brain or high doses of certain chemotherapy drugs. Some survivors may struggle with memory, attention, and problem-solving, which can affect their performance in school in future careers.¹ These cognitive challenges can range from mild to severe, sometimes requiring special accommodations in educational or work settings.

The endocrine system — which controls hormones and growth — is also highly sensitive to cancer treatments. Radiation near the brain or chemotherapy that affects hormone production can lead to growth delays, early or delayed puberty, and thyroid disorders. Some survivors may develop fertility issues later in life due to damage to the reproductive organs, making family planning more complicated.¹

In addition to physical challenges, many childhood cancer survivors face emotional and mental health struggles. Experiencing cancer at a young age — in addition to concerns about long-term health risks — can lead to anxiety, depression, and post-traumatic stress disorder.¹ Social challenges such as feeling different from peers or dealing with the lasting effects of treatment on physical appearance can further impact self-esteem and emotional well-being.

The Role of Genomics in Predicting Late Effects

Genomics is changing the way people understand childhood cancer survivorship by identifying genetic factors that influence long-term health risks. By analyzing a survivor’s genetic makeup alongside their treatment history, researchers can predict which effects they may develop and tailor their care accordingly.

Why Do Some Survivors Experience More Late Effects Than Others?

Not all childhood cancer survivors face the same long-term health challenges. Some experience severe complications, while others have relatively few. This difference has led researchers to explore the role of genomics — the study of genes and how they influence health — in predicting which survivors are most at risk for late effects.²

Cancer treatments like chemotherapy and radiation don’t affect everyone in the same way. A person’s genetic makeup can influence how their body processes these treatments and whether they're more vulnerable to certain complications. For example, some survivors have genetic markers that make them more likely to develop heart disease after exposure to specific chemotherapy drugs.

Others may be genetically predisposed to cognitive issues following radiation therapy. Some may be more likely to develop a second cancer later in life.³ By identifying these genetic risk factors, healthcare providers can better anticipate which late effects survivors may face and take preventive action.

According to lead investigator of an NIH-led study Todd M. Gibson, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics, “Knowledge about a person’s genetic makeup could potentially be useful in managing their risk of subsequent cancers. The hope would be that, in the future, we can incorporate genetics along with treatment exposures and other risk factors to provide a more complete picture of a survivor’s risk of subsequent cancers to help guide their long-term follow-up care.” [SOURCE: https://www.nih.gov/news-events/news-releases/childhood-cancer-survivors-inherited-genetic-factors-influence-risk-cancers-later-life ]³

Personalized Follow-Up Care Based on Genetics

One of the biggest advantages of genomics is the ability to provide personalized follow-up care. Instead of a one-size-fits-all approach, healthcare professionals can create tailored health plans based on someone’s genetic risk profile.⁴

For instance, a survivor with a higher genetic risk for heart damage could undergo more frequent cardiac screenings and adopt heart-healthy lifestyle habits early on. Similarly, those at risk for secondary cancers could receive regular monitoring to catch potential issues at the earliest stage.

The St. Jude Survivorship Portal is a powerful example of how genomics is shaping childhood cancer survivorship. Developed by St. Jude Children’s Research Hospital, this open-access platform is the first data portal designed to analyze and visualize pediatric cancer survivorship data. It integrates clinical and genomic information, including treatment exposures, whole-genome sequencing, and long-term outcomes.

With data from over 7,700 survivors, it helps researchers and healthcare providers identify genetic factors that contribute to late effects, enabling more precise and proactive care.⁵ This kind of individualized care allows survivors to take proactive steps to protect their long-term health.

Using Genomics to Improve Treatment Decisions

Beyond predicting late results, genomics is also shaping the way healthcare providers approach cancer treatment. If genetic testing reveals a child is more susceptible to long-term complications, healthcare professionals may be able to adjust.

The treatment plan could involve choosing drugs or radiation doses that are less likely to trigger lasting harm. This kind of precision medicine has the potential to improve both survival rates and long-term quality of life.⁶

Possible Challenges in Using Genomics to Predict Late Effects

While genomics offers exciting possibilities, it also comes with challenges, including the complexity of genetic interactions, accessibility of testing, and ethical considerations. Ensuring all survivors benefit from these advancements requires overcoming barriers in research, healthcare integration, and data security.

Complexity of Genetic Influence

While genomics has the potential to revolutionize childhood cancer survivorship, predicting late effects isn’t always straightforward. Many arise from a combination of genetic, environmental, and treatment-related factors.

A survivor’s lifestyle, overall health, and even unknown genetic interactions can all play a role in late effects.⁷ This complexity makes it difficult to pinpoint which individuals will develop them, even when genetic risk factors are identified.

Accessibility and Cost

Another challenge is not all survivors have access to genetic testing and personalized follow-up care.⁸ While large institutions like St. Jude are leading the way in integrating genomics into survivorship care, not all hospitals and clinics have the resources to provide genetic screening or advanced risk assessment.

Insurance coverage for genetic testing can also be inconsistent, making it difficult for some survivors to benefit from these advancements.

Ethical Considerations and Psychological Impact

Genomic testing can also reveal genetic predispositions to other health conditions, including diseases unrelated to childhood cancer. This raises ethical concerns about how much information should be shared with survivors and their families.

Knowing one’s genetic risks can also lead to anxiety, especially if there are no clear prevention or treatment options available.⁸ Balancing the benefits of genetic knowledge with the emotional and ethical implications is an ongoing challenge.

Data Privacy and Security

With massive amounts of genetic and clinical data being collected, protecting patient privacy is a major concern. Strict safeguards must be in place to ensure sensitive information remains secure. Maintaining trust among survivors and their families is essential as genomic research continues to expand.

The Need for More Research

Genomics is still a developing field, and while researchers have identified some genetic markets linked to late effects, many remain unknown. Ongoing studies and larger datasets are necessary to improve predictions and make genomic-driven care a standard part of survivorship planning.

Collaboration between researchers, healthcare professionals, and policymakers will be key to making these advancements widely available.

Future Implications of Genomics in Childhood Cancer Survivorship

As genomic research progresses, the potential for personalized survivorship care continues to grow. From early interventions to precision medicine, these advancements could revolutionize how survivors manage their long-term health, leading to better outcomes.

The Impact of Fundraising on Survivorship Research

Funding is an essential part of advancing research and improving childhood cancer survivorship. Many organizations work tirelessly to support these efforts, ensuring survivors receive better long-term care. For example, THON — a student-run philanthropy at Penn State — hosts an annual 46-hour dance marathon to raise money for the Four Diamonds Fund, which supports pediatric cancer research and care. In 1993 alone, THON made history by raising over $1 million to help children with cancer.⁹

Fundraisers like this not only provide financial support for critical research but also raise awareness about the long-term needs of survivors. This helps drive future breakthroughs in genomics and survivorship care.

More Accurate Predictions and Personalized Care

As genomic research advances, the ability to predict late effects with greater accuracy will continue to improve. With larger datasets and more sophisticated analysis tools, scientists will be able to identify new genetic markers linked to specific health risks. This means survivors could receive even more personalized follow-up care, with targeted screening schedules and preventive measures based on their unique genetic profiles.

Early Interventions and Preventive Strategies

With better risk prediction, interventions can start earlier.¹⁰ For example, if a survivor is found to have a high genetic risk for heart disease due to their cancer treatment, healthcare providers can recommend lifestyle modifications, medications, or even new therapies to reduce the risk before symptoms appear.

The same approach could apply to cognitive effects, secondary cancers, and metabolic conditions, helping survivors maintain better long-term health.

Integration into Standard Healthcare

Currently, genomic testing is mostly used in specialized research settings, but in the future, it could become a routine part of survivorship care. Pediatric oncology clinics and primary care providers may incorporate genetic risk assessments into standard follow-up plans. This would allow survivors to get tailored medical advice no matter where they receive care, not just at major cancer centers.

Advancements in Treatment Approaches

By understanding how genetic factors influence the body’s response to therapy, scientists could develop less toxic treatment options that reduce the risk of long-term complications. Precision medicine could allow healthcare professionals to select the most effective and least harmful treatment for each patient, improving survival rates and quality of life.

Moving Forward

The field of survivorship science is growing. More hospitals and research centers are investing in genomic studies to improve care for survivors.

While there’s still much to learn, one thing is clear — genomics is changing the future of childhood cancer survivorship and is giving survivors the best chance at a healthy life.

References

1. Late effects of treatment for childhood cancer. Cancer.gov. February 12, 2025. https://www.cancer.gov/types/childhood-cancers/late-effects-pdq
2. Cancer-related genomic testing and genetic testing. American Cancer Society. November 2, 2023. https://www.cancer.org/cancer/understanding-cancer/genes-and-cancer/genomic-genetic-testing.html
3. For childhood cancer survivors, inherited genetic factors influence. National Institutes of Health. March 11, 2024. https://www.nih.gov/news-events/news-releases/childhood-cancer-survivors-inherited-genetic-factors-influence-risk-cancers-later-life
4. Singh D, Dhiman VK, Pandey M, et al. Personalized medicine: An alternative for cancer treatment. Cancer Treatment and Research Communications. December 20, 2024. doi:10.1016/j.ctarc.2024.100860
5. Jude survivorship portal brings researchers ‘one-click’ away from discovery. St. Jude Children’s Research Hospital. April 9, 2024. https://www.stjude.org/media-resources/news-releases/2024-medicine-science-news/survivorship-portal-brings-researchers-one-click-away-from-discovery.html
6. Genomics: how unlocking our genes is transforming healthcare. Wellcome. January 29, 2025. https://wellcome.org/news/genomics-how-unlocking-our-genes-transforming-healthcare
7. Late and long-term effects of cancer. American Cancer Society. May 29, 2024. https://www.cancer.org/cancer/survivorship/long-term-health-concerns/long-term-side-effects-of-cancer.html
8. Pinzón-Espinosa J, Van Der Horst M, Zinkstok J, et al. Barriers to genetic testing in clinical psychiatry and ways to overcome them: from clinicians’ attitudes to sociocultural differences between patients across the globe. Translational Psychiatry. October 11, 2022. doi:10.1038/s41398-022-02203-6
9. New generations continue the fight against childhood cancer. THON.org. October 17, 2024. https://thon.org/blog/new-generations-continue-the-fight/
10. MacDuffie KE, Cohn B, Appelbaum P, et al. Early Intervention services in the era of genomic medicine: setting a research agenda. Pediatric Research. October 22, 2024. doi:10.1038/s41390-024-03668-5