The art of war: using genetic insights to understand and harness radiation sensitivity in hematologic malignancies

Sep 23, 2026

This review examines hematologic malignancies through the lens of radiosensitivity, integrating the known genomic landscape with radiation oncology practice. It traces how historical advances in understanding radiosensitivity connect to discovery and clinical implications of mutated genes central to DNA repair, including TP53 and ATM. The work highlights how radiogenomics may improve personalized medicine by predicting radiotherapy response and toxicity, while outlining practical barriers such as alteration heterogeneity and the need for standardized protocols and decision support systems.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

What is biologic radiosensitivity and radioresponsiveness?

Genetic insights and pivotal mutated genes

Radiogenomics: predicting response and toxicity

Integrating genomic data into clinical practice

TYPE Review PUBLISHED 21 March 2025 DOI 10.3389/fonc.2024.1478078 OPEN ACCESS EDITED BY Thomas FitzGerald, University of Massachusetts Boston, United States REVIEWED BY Lara Hilal, American University of Beirut Medical Center, Lebanon Ji Hyun Hong, The Catholic University of Korea, Republic of Korea Jonathan Leeman, Brigham and Women’s Hospital and Harvard Medical School, United States *CORRESPONDENCE N. Ari Wijetunga [wij@email.unc.edu](wij@email.unc.edu) RECEIVED 09 August 2024 ACCEPTED 20 November 2024 PUBLISHED 21 March 2025 CITATION Wijetunga NA, Yahalom J and Imber BS (2025) The art of war: using genetic insights to understand and harness radiation sensitivity in hematologic malignancies. Front. Oncol. 14:1478078 . doi: 10.3389/fonc.2024.1478078 COPYRIGHT © 2025 Wijetunga, Yahalom and Imber. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The art of war: using genetic insights to understand and harness radiation sensitivity in hematologic malignancies N. Ari Wijetunga 1*, Joachim Yahalom 2 and Brandon S. Imber 2 1 Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, United States, 2 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, United States It is well established that hematologic malignancies are often considerably radiosensitive, which enables usage of far lower doses of therapeutic radiotherapy. This review summarizes the currently known genomic landscape of hematologic malignancies, particularly as it relates to radiosensitivity and the ﬁeld of radiation oncology. By tracing the historical development of the modern understanding of radiosensitivity, we focus on the discovery and implications of pivotal mutated genes in hematologic malignancies such as TP53, ATM, and other genes critical to DNA repair pathways. These genetic insights have contributed signiﬁcantly to the advancement of personalized medicine, aiming to enhance treatment precision and outcomes, and there is an opportunity to extend these insights to personalized radiotherapy. We explore the transition from early discoveries to the current efforts in integrating comprehensive genomic data into clinical practice. Speciﬁc examples from Hodgkin lymphoma, non-Hodgkin lymphoma, and plasma cell neoplasms illustrate how genetic mutations could inﬂuence radiosensitivity and impact subsequent radiotherapeutic response. Despite the advancements, challenges remain in translating these genetic insights into routine clinical practice, particularly due to the heterogeneity of alterations and the complex interactions within cancer signaling pathways. We emphasize the potential of radiogenomics to address these challenges by identifying genetic markers that predict radiotherapy response and toxicity, thereby reﬁning treatment strategies. The need for robust decision support systems, standardized protocols, and ongoing education for healthcare providers is critical to the successful integration of genomic data into radiation therapy. As research continues to validate genetic markers and explore novel therapeutic combinations, the promise of personalized radiotherapy becomes increasingly attainable, offering the potential to signiﬁcantly improve outcomes for patients with hematologic malignancies. KEYWORDS hematologic malignances, personalized medicine, radiation therapy, precision oncology, genomics, lymphoma Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) Introduction “Know your enemy and know yourself, and you can ﬁght a hundred b

FAQs

What is the central focus of this review on hematologic malignancies?

The review focuses on how genomic insights explain and influence radiosensitivity, and how this knowledge can be used to personalize radiotherapy decisions.

Which types of genes are highlighted as important for radiation response?

Key examples include genes such as TP53 and ATM, especially those involved in DNA repair pathways that affect response to radiation.

What challenges must be solved to integrate genetic insights into routine radiotherapy?

Challenges include heterogeneity of genetic alterations and complex interactions within cancer signaling pathways, alongside the need for robust decision support systems and standardized protocols.

Sep 23, 2026

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