All for one, though not one for all: team players in normal tissue radiobiology

Abstract

Purpose

As part of the special issue on ‘Women in Science’, this review offers a perspective on past and ongoing work in the field of normal (non-cancer) tissue radiation biology, highlighting the work of many of the leading contributors to this field of research. We discuss some of the hypotheses that have guided investigations, with a focus on some of the critical organs considered dose-limiting with respect to radiation therapy, and speculate on where the field needs to go in the future.

Conclusions

The scope of work that makes up normal tissue radiation biology has and continues to play a pivotal role in the radiation sciences, ensuring the most effective application of radiation in imaging and therapy, as well as contributing to radiation protection efforts. However, despite the proven historical value of preclinical findings, recent decades have seen clinical practice move ahead with altered fractionation scheduling based on empirical observations, with little to no (or even negative) supporting scientific data. Given our current appreciation of the complexity of normal tissue radiation responses and their temporal variability, with tissue- and/or organ-specific mechanisms that include intra-, inter- and extracellular messaging, as well as contributions from systemic compartments, such as the immune system, the need to maintain a positive therapeutic ratio has never been more urgent. Importantly, mitigation and treatment strategies, whether for the clinic, emergency use following accidental or deliberate releases, or reducing occupational risk, will likely require multi-targeted approaches that involve both local and systemic intervention. From our personal perspective as five ‘Women in Science’, we would like to acknowledge and applaud the role that many female scientists have played in this field. We stand on the shoulders of those who have gone before, some of whom are fellow contributors to this special issue.

Keywords:

• Normal tissue radiobiology
• immune system
• lung
• cardiovascular system
• brain

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. The opinions and assertions expressed herein are those of the authors and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense.

Additional information

Funding

Dr. Boerma’s work was supported by National Institute of General Medical Sciences (NIGMS) P20 GM109005; National Institute of Allergy and Infectious Diseases (NIAID) U01 AI148308 and U01 AI133561. Dr. Davis’ work was supported by National Aeronautics and Space Administration (NASA) 80NSSC18K1080. Dr. Jackson’s work was supported by Biomedical Advanced Research and Development Authority (BARDA) HHSO10020150009I, HHSO1003300IT, HHSO10033003T, and HHSO10033004T; NIAID R44AI138865, and U19 AI150574. Dr. Schaue’s work was supported by the National Cancer Institute (NCI) R01 CA226875, R01 CA238998, and R21 CA228542; NIAID U01 AI148322. Dr. Williams’ work was supported by NCI R01 CA220467, R01 HL127001; NASA 80NSSC21K0542.

Notes on contributors

Marjan Boerma

Marjan Boerma is an Associate Professor in Pharmaceutical Sciences at the University of Arkansas for Medical Sciences (UAMS), and the director of the College of Pharmacy Division of Radiation Health and the Center for Studies of Host Response to Cancer Therapy. Her research focuses on cancer survivorship issues, particularly radiation-induced heart disease, risks of cardiovascular disease from exposure to radiation during space travel, and the development of medical countermeasures against nuclear accidents or terrorism

Catherine M. Davis

Catherine M. Davis is an Assistant Professor of Pharmacology and Molecular Therapeutics at the Uniformed Services University of the Health Sciences and a member of the Scientific Research Department at the Armed Forces Radiobiology Research Institute. Her research focuses on radiation-induced cognitive dysfunction, primarily addressing risks to the central nervous system from radiation exposure during space travel or military operations.

Isabel L. Jackson

Isabel L. Jackson is an Associate Professor in Radiation Oncology and Director of the Division of Translational Radiation Sciences (DTRS) at the University of Maryland. Dr. Jackson is a subject matter expert in the field of tumor and normal tissue radiobiology, with specialized expertise in medical countermeasure (MCM) development for acute radiation sickness and delayed effects of acute radiation exposure.

Dörthe Schaue

Dörthe Schaue is an Associate Professor in the Department of Radiation Oncology at the University of California Los Angeles. Her research interests include tumor-specific immune responses in the context of radiation therapy, radiation-induced normal tissue responses, immune imbalances, inflammaging and countermeasure development.

Jacqueline P. Williams

Jacqueline P. Williams is a Professor in the Departments of Environmental Medicine and Radiation Oncology at the University of Rochester. Her research interests include investigation of the normal tissue effects that follow high dose (therapy- or accident-related) or low dose (space travel-related) irradiation, with a focus on lung, skin, bone marrow and CNS effects.