학술논문

Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment.
Document Type
Article
Source
Cancers. Nov2023, Vol. 15 Issue 22, p5314. 22p.
Subject
*GENETIC mutation
*GENOMICS
*RADIATION-sensitizing agents
*DECISION making
*TUMOR markers
*ONCOLOGY
Language
ISSN
2072-6694
Abstract
Simple Summary: Genetic information is seldom incorporated in formulating radiation treatment recommendations for patients with cancer, even though genetic information is now well established to be prognostic and predictive of cancer outcomes and response to systemic therapy. With the increasing accessibility to and use of genetic testing, tumor, and germline genetic data have the potential to inform clinical decisions by improving the efficacy of radiation treatment and ensuring the safety of treatment delivery. This review summarizes the biological underpinning of "radio-sensitizing genes", discusses the clinical basis and evidence for identifying genetic mutations as radiation response biomarkers, and proposes future directions for research as well as clinical implementation. Radiation treatment (RT) is a mainstay treatment for many types of cancer. Recommendations for RT and the radiation plan are individualized to each patient, taking into consideration the patient's tumor pathology, staging, anatomy, and other clinical characteristics. Information on germline mutations and somatic tumor mutations is at present rarely used to guide specific clinical decisions in RT. Many genes, such as ATM, and BRCA1/2, have been identified in the laboratory to confer radiation sensitivity. However, our understanding of the clinical significance of mutations in these genes remains limited and, as individual mutations in such genes can be rare, their impact on tumor response and toxicity remains unclear. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN), provide limited guidance on how genetic results should be integrated into RT recommendations. With an increasing understanding of the molecular underpinning of radiation response, genomically-guided RT can inform decisions surrounding RT dose, volume, concurrent therapies, and even omission to further improve oncologic outcomes and reduce risks of toxicities. Here, we review existing evidence from laboratory, pre-clinical, and clinical studies with regard to how genetic alterations may affect radiosensitivity. We also summarize recent data from clinical trials and explore potential future directions to utilize genetic data to support clinical decision-making in developing a pathway toward personalized RT. [ABSTRACT FROM AUTHOR]