Overcoming Dedifferentiation of Pediatric Thyroid Cancer Through Molecularly Targeted Therapy
Abstract
The work outlined in this application addresses the Fiscal Year 2021 (FY20) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas of (1) thyroid cancer and (2) cancer in children, adolescents and young adults. Thyroid cancer is the most common endocrine cancer in children, and incidences are steadily increasing. Fortunately, thyroid cancer has a low mortality rate; however, patients often suffer from long-term consequences of therapy. Further, a small subset of pediatric thyroid cancer patients have tumors that spread to their lungs and a majority of these patients are never cured of their disease. Better treatments are needed for these children. While remarkable advances have been made in many pediatric cancers, pediatric thyroid cancer has seen very few new therapies or advances in standard of care. Addressing the need for the rational design of targeted therapies for pediatric thyroid cancer is the overarching focus of our work. Our work addresses the Military Relevance Focus Area: (1) Mission Readiness: Gaps in cancer prognosis and treatment. Successful completion will help mitigate the impact of cancer on military personnel, their families, and the American public. Pediatric thyroid cancer is the second most common cancer diagnosed in teenaged girls. Incidence rates are steadily increasing and is associated with exposure to radiation in early childhood. Compared to adults, pediatric thyroid cancer is more likely to spread and reoccur. The stress of having a critically ill child impacts the military readiness of Armed Forces family members. Knowing that their children and AYA dependents will receive the highest standard in care provides invaluable peace of mind for our active and reserve military personnel, allowing our soldiers, airman, and sailors to focus their full attention on their military mission. Thyroid cancer patients with disease that has spread to other parts of the body are often treated with radioactive iodine to selectively kill thyroid cancer cells. Thyroid cells are unique in their ability to pick up iodine, so this is a very targeted therapy that can help to prevent damage to non-tumor cells. However, as thyroid cancer progresses, the tumor cells change, and lose the ability to absorb iodine and therefore become resistant to therapy. In adult thyroid tumors, it has been shown that treating patients with targeted therapy can allow thyroid tumor cells to start absorbing iodine again, and therefore become sensitive to radioactive iodine treatment. In this proposal, we will determine whether pediatric thyroid cancer patients respond similarly to adult patients and determine how these targeted therapies change the tumor cells so that they can absorb iodine. This work will be the first to define how the genetics and molecular profile of pediatric and adult thyroid cancers are different and how we can exploit these differences to more effectively treat pediatric thyroid cancer patients. Working with the Child and Adolescent Thyroid Cancer Consortium will allow us to profile samples from patients around the country and to expand our clinical trials to more sites in the future. This work could be paradigm shifting and allow us to more precisely tailor our therapy to prevent treatment associated side-effects that impact quality of life for childhood cancer survivors. The FY21 PRCRP TTSA encourages addressing Overarching Challenges in cancer research. Our work will seek to (1) Identify and understand the unique and novel features driving cancer presentation to improve outcomes across the spectrum. Pediatric and adult thyroid cancers behave differently despite sharing the same genetic mutations and we will dissect how pediatric tumors respond to molecularly targeted therapy, (2) transform cancer treatment through new targets for advanced disease (metastatic) and limit therapy-associated toxicity, and (3) identify and understand the mechanism behind cancer genetic basis. We will
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210654
Entities
People
- Theodore Laetsch
Organizations
- United States Army