Kids Cancer CEO (Community Engagement & Outreach) : Differences between adult and pediatric cancers – Molecular Oncology Series

Molecular Oncology Series

Patient response to cancer malignancies differs significantly from one patient to the next. These differences can be attributed to the patient’s case-by-case scenario in terms of co-morbidities, location of the tumor, and what stage the cancer is in when it is discovered, as a few examples. Adding to these differences, cancers themselves are markedly different in how the tumor acts on a cellular level, which can significantly impact how the whole tumor responds to different treatments. These differences between cancers at the cellular level can be attributed to the cancer cell’s molecular biology.

What is Molecular Oncology?

Utilizing how cancer works on both the cellular and prognostic levels is a relatively new advancement in oncology, starting in the mid-twentieth century. The benefit of understanding how cells function at the molecular level became evident by work from Sidney Farber. Dr. Farber showed that blocking folic acid production helped slow down bone marrow cell growth and induced temporary remission in childhood leukemias (1). This work revolutionized how scientists approached the cancer field and instigated the development of molecular oncology. Molecular oncology uses basic science, such as molecular and genetic cancer differences, to drive therapeutic interventions (2). In this blog post, we will be discussing the critical differences in pediatric and adult molecular oncology.

Is there a genomic difference between pediatric and adult cancers?

One of the critical molecular differences between pediatric and adult cancers is their genomic landscape. Pediatric tumors contain substantially lower DNA mutations than adult cancers (3). It is still unknown why pediatric tumors have a decreased mutational burden than adult cancers. However, one reason could be a decreased external or environmental impact on pediatric patients instead of adult patients. Some of these environmental impacts that can compound to create mutations in adult patients include UV light damage from the sun, stress, diet, and smoking or drinking habits. Translating this molecular difference between pediatric and adult cancers to how it affects therapeutic development, a lack of mutations in pediatric cancers makes it more difficult to find a selective, druggable target.

A cancer mutation can affect a protein (or protein pathway) that is hyperactive or required in the cancer cell but not hyperactive or minimally expressed in normal cells. In this case, a drug targeting the protein required in the cancer cell will not have as many side effects in the patient. For pediatric cancers, the issue can be thought of as a driverless car problem: if you have no driver (mutation), then what other methods can you use to stop the vehicle (cancer)? You can target the engine or the tires, but these are critical systems that will affect other cars (non-cancerous cells). This can lead to toxic side effects in the patient (4).

Does chemotherapy affect pediatric and adult patients differently?

Another critical difference between pediatric and adult cancers is that pediatric cancer patients have more severe long-term side effects to standard therapies as opposed to adult patients. This is because the standard cancer therapy kills the cancer cells but is also toxic to normal cells. Sometimes, this toxicity presents itself much later or accumulates throughout the years. For example, whereas an adult patient might not encounter some of the issues that could present from chemotherapy treatment 40 years down the line since they started their treatment at age 50, a pediatric cancer patient could be encountering the issue at the age of 50 if they had chemotherapy treatment at the age of 10.

What are some future goals for clinicians and researchers?

Overall, the above are just some of the issues cancer researchers are considering to help develop new therapeutics for pediatric cancer patients. There is a greater need for targeted therapies in pediatric cancer patients, though this can be a catch-22 as it is also more difficult to develop targeted therapies for pediatric cancers. Understanding the molecular landscape of pediatric cancers can be critical in this development, and researchers working together with clinicians can help move the field forward to discover targeted and, thus, less toxic therapies for children’s cancer treatment.

This article was written by Aiola Stoja, PhD student at UT Health San Antonio, at the Greehey Children’s Cancer Research Institute (GCCRI). This article is a part of the “Molecular Oncology” series of the Kid’s Cancer Community Engagement and Outreach group at GCCRI. This series aims to explain how molecular aspects of cancer, significant at the cellular level, can impact the therapy and patient prognosis at the clinical level.

Reviewed by Greehey CCRI Principal Investigator Alexander Bishop, DPhil

Contact Aiola with any questions at stoja@uthscsa.edu

• References and Further Reading
  Milestones in Cancer Research and Discovery. (2020, August 31). National Cancer Institute. https://www.cancer.gov/research/progress/250-years-milestones
• Bronchud, H., M., Foote, M., Giaccone, G., Olopade, O., & Workman, P. (Eds.). (2008). Principles of Molecular Oncology (3rd ed.). Humana Press Inc.
• Sweet-Cordero, E. A., & Biegel, J. A. (2019). The genomic landscape of pediatric cancers: Implications for diagnosis and treatment. Science (New York, N.Y.), 363(6432), 1170–1175. https://doi.org/10.1126/science.aaw3535
• Kattner, P., Strobel, H., Khoshnevis, N., Grunert, M., Bartholomae, S., Pruss, M., Fitzel, R., Halatsch, M.-E., Schilberg, K., Siegelin, M. D., Peraud, A., Karpel-Massler, G., Westhoff, M.-A., & Debatin, K.-M. (2019). Compare and contrast: pediatric cancer versus adult malignancies. Cancer Metastasis Reviews, 38(4), 673–682. https://doi.org/10.1007/s10555-019-09836-y

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Since 2004, UT Health San Antonio, Greehey Children’s Cancer Research Institute’s (Greehey CCRI) mission has been to advance scientific knowledge relevant to childhood cancer, contribute to understanding its causes, and accelerate the translation of knowledge into novel therapies. Greehey CCRI strives to have a national and global impact on childhood cancer by discovering, developing, and disseminating new scientific knowledge. Our mission consists of three key areas — research, clinical, and education.

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