Posted: April 30th, 2022

A Personalized Approach in Childhood Cancer Treatment

A Personalized Approach in Childhood Cancer Treatment

Cancer treatment in children has advanced significantly in recent decades. Where survival rates were once dismal, many childhood cancers now have cure rates over 80% (American Cancer Society, 2022). However, not all children respond equally well to standard treatment protocols, which typically involve combinations of chemotherapy, surgery, and radiation therapy. Some experience cancer recurrence or develop treatment-related complications like secondary cancers later in life. A personalized approach aims to optimize outcomes for each child by tailoring therapy based on the unique characteristics of their individual tumor. Genomic testing helps identify molecular markers that can guide more targeted and less toxic treatment selection (Parsons et al., 2020). This paper will explore advances in personalized medicine for childhood cancer and how a precision oncology approach may improve survival and quality of life for pediatric cancer patients.
Genomic Testing to Guide Therapy
Next-generation sequencing allows comprehensive molecular profiling of a child’s tumor to detect genetic mutations and abnormalities that may be driving cancer growth (Giaccone et al., 2020). Certain mutations indicate whether a tumor is likely to respond to specific targeted drugs. For example, the BCR-ABL1 fusion gene caused by the Philadelphia chromosome is a driver of chronic myeloid leukemia (CML) (American Cancer Society, 2022). Testing helps determine if a child with CML is a candidate for tyrosine kinase inhibitors like imatinib, which block BCR-ABL1’s activity and have improved outcomes for this once fatal disease (National Cancer Institute, 2022). In other cancers, genomic testing may reveal fusions, amplifications or mutations in genes like ALK, NTRK, ROS1 or BRAF that can be targeted (Parsons et al., 2020; Giaccone et al., 2020). This allows children to receive targeted therapies matched to the molecular abnormalities in their individual tumors.
Risk Stratification for Treatment Intensity

Not all childhood cancers carry the same risk of relapse or treatment failure. Genomic profiling can also aid in risk stratification, helping determine which patients require more intensive treatment versus those who may do well with de-escalated therapy and fewer side effects (Giaccone et al., 2020). In neuroblastoma, for example, patients with low-risk disease five-year survival exceeds 90% with surgery alone, while high-risk patients require intensive multi-agent chemotherapy and stem cell transplantation (American Cancer Society, 2022). Genomic testing identifies high-risk features like MYCN amplification and segmental chromosomal abnormalities to guide management (National Cancer Institute, 2022). Similarly, stratifying leukemia patients according to cytogenetic and molecular characteristics helps tailor therapy intensity (American Society of Clinical Oncology, 2022). This precision approach aims to avoid over- or under-treatment for each child.
Immunotherapies and Cellular Therapies
Advances in immunotherapy and cellular therapies also enable more personalized cancer treatment. Chimeric antigen receptor (CAR) T-cell therapy harnesses the power of a child’s own immune cells to target specific tumor antigens (Giaccone et al., 2020). After genetically engineering T-cells to express a CAR targeting CD19, CD22 or other antigens highly expressed in leukemia and lymphoma cells, the modified cells are infused back into the patient where they multiply and induce durable remissions in some children with few treatment options left (American Cancer Society, 2022; National Cancer Institute, 2022). Ongoing research aims to expand CAR T-cell therapy to additional pediatric solid tumors. Other cellular therapies under investigation include natural killer cells, T-cell receptors, and oncolytic viruses engineered to selectively target and kill cancer cells (Giaccone et al., 2020). As these novel immunotherapies continue advancing, they hold promise to transform outcomes for select childhood cancer patients.
Conclusion
A personalized approach utilizing comprehensive genomic profiling, risk stratification, and novel targeted and cellular therapies has the potential to optimize outcomes for children with cancer. Identifying molecular markers that drive individual tumors allows selection of the most appropriate targeted drugs or immunotherapies for each child. This precision oncology approach aims to improve survival and quality of life by delivering the right treatment at the right intensity for each patient. Continued research expanding our understanding of cancer genetics and immunotherapy promises to transform pediatric oncology and bring new hope to children with cancer.
References
American Cancer Society. (2022). Key statistics for childhood cancers. https://www.cancer.org/cancer/cancer-in-children/key-statistics.html
American Society of Clinical Oncology. (2022). Cancer.net: Childhood acute lymphoblastic leukemia treatment. https://www.cancer.net/cancer-types/leukemia-acute-lymphoblastic-all-childhood/treatment
Giaccone, G., et al. (2020). Personalized pediatric oncology and immune therapies: Rather customize than randomize. Frontiers in Oncology, 10. https://doi.org/10.3389/fonc.2020.00377
National Cancer Institute. (2022). Neuroblastoma treatment (PDQ®)–patient version. https://www.cancer.gov/types/neuroblastoma/patient/neuroblastoma-treatment-pdq
Parsons, D. W., et al. (2020). Advancements in childhood cancer move toward personalized treatments. The Voice, 25(2). https://voice.ons.org/advocacy/advancements-in-childhood-cancer-move-toward-personalized-treatments

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