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Live Imaging to Quantify Cellular Radiosensitivity in Patient-Derived Tumor Organoids

Live Imaging to Quantify Cellular Radiosensitivity in Patient-Derived Tumor Organoids

Published on: April 5, 2024

Microenvironmental remodeling in FLASH radiotherapy.

Yubo Zhao¹, Hang Li², Jiaqiao Zhong¹

¹Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Frontiers in Cell and Developmental Biology

|July 16, 2026

Summary

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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Ultra-high dose rate radiation (FLASH-RT) shows promise for cancer therapy by sparing normal tissues while controlling tumors. This review explores its physical, chemical, and biological effects on the tumor microenvironment.

Area of Science:

Oncology
Radiation Oncology
Biophysics

Background:

Ultra-high dose rate radiation (FLASH-RT) offers a potential therapeutic advantage by sparing normal tissues.
Understanding the physical-chemical-biological continuum of FLASH-RT is crucial for its clinical application.

Purpose of the Study:

To propose a microenvironment-centered framework for interpreting FLASH-RT.
To integrate evidence on physical aspects, normal tissue responses, tumor control, and biological mechanisms of FLASH-RT.

Main Methods:

Review of preclinical and early clinical studies on FLASH-RT.
Analysis of physical prerequisites, organ-specific responses, and tumor control outcomes.
Integration of data on biological mechanisms and microenvironmental remodeling.

Keywords:

FLASH radiotherapy immune microenvironment microenvironmental remodeling normal-tissue sparing radiation biology radiosensitization redox biology ultra-high dose rate radiotherapy

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Main Results:

FLASH-RT can attenuate inflammation, preserve regenerative capacity, reduce DNA damage, and mitigate fibrosis in normal tissues.
Tumor control with FLASH-RT is comparable to conventional radiotherapy in preclinical models.
Early clinical studies indicate feasibility and preliminary safety of FLASH-RT.

Conclusions:

FLASH-RT-induced microenvironmental remodeling involves altered oxygen/radical dynamics, immune modulation, and preserved homeostasis.
Responses are context-dependent, influenced by radiation parameters and tissue type.
Standardized dosimetry and paired tumor-normal tissue evaluations are vital for clinical translation.