Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May:68 Suppl 2:e28439.
doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges

Ralph Vatner  1 , Charles D James  2 , Vythialingam Sathiaseelan  3 , Kathryn M Bondra  4 , John A Kalapurakal  3 , Peter J Houghton  4
Affiliations
Review

Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges

Ralph Vatner et al. Pediatr Blood Cancer. 2021 May.

Abstract

Despite radiation therapy (RT) being an integral part of the treatment of most pediatric cancers and the recent discovery of novel molecular-targeted agents (MTAs) in this era of precision medicine with the potential to improve the therapeutic ratio of modern chemoradiotherapy regimens, there are only a few preclinical trials being conducted to discover novel radiosensitizers and radioprotectors. This has resulted in a paucity of translational clinical trials combining RT and novel MTAs. This report describes the opportunities and challenges of investigating RT together with MTAs in preclinical testing for immunotherapy, brain tumors, and sarcomas in pediatric oncology. We discuss the need for improving the collaboration between radiation oncologists, biologists, and physicists to improve the reliability, reproducibility, and translational potential of RT-based preclinical research. Current translational clinical trials using RT and MTAs for immunotherapy, brain tumors, and sarcomas are described. The technologic advances in experimental RT, availability of novel experimental tumor models, advances in immunology and tumor biology, and the discovery of novel MTAs together hold considerable promise for good quality preclinical and clinical multimodality research to improve the current rates of survival and toxicity in children afflicted with cancer.

Trial registration: ClinicalTrials.gov NCT00356031 NCT02050919 NCT02180867 NCT03116529 NCT03463408 NCT03217266 NCT02787642 NCT04220229 NCT03868852 NCT03361436 NCT02275286.

Keywords: brain tumors; immunotherapy; molecular-targeted agents; physics; radiation therapy; sarcomas.

PubMed Disclaimer

References

REFERENCES

    1. Breneman JC, Donaldson SS, Constine L, et al. The Children's Oncology Group radiation oncology discipline: 15 years of contributions to the treatment of childhood cancer. Int J Radiat Oncol Biol Phys. 2018;101:860-874.
    1. Thomas PR, Tefft M, Compaan PJ, Norkool P, Breslow NE, D'Angio GJ. Results of two radiation therapy randomizations in the third National Wilms' Tumor Study. Cancer. 1991;68(8):1703-1707.
    1. Dix DB, Gratias EJ, Seibel N, et al. Omission of lung radiation in patients with stage IV favorable histology Wilms tumor showing complete long nodule response after chemotherapy: a report from the Children's Oncology Group AREN0533 study. J Clin Oncol. 2015;33:10011-10011.
    1. Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average risk medulloblastoma. J Clin Oncol. 2006;24(25):4202-4208.
    1. Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014;32(32):3651-3658.

Substances

Associated data