Abstract
Radiation therapy (RT) has been employed as a tumoricidal modality for more than 100 years and on 470,000 patients each year in the United States. The ionizing radiation causes genetic changes and results in cell death. However, since the biological mechanism of radiation remains unclear, there is a pressing need to understand this mechanism to improve the killing effect on tumors and reduce the side effects on normal cells. DNA break and epigenetic remodeling can be induced by radiotherapy. Hence the modulation of histone modification enzymes may tune the radiosensitivity of cancer cells. For instance, histone deacetylase (HDAC) inhibitors sensitize irradiated cancer cells by amplifying the DNA damage signaling and inhibiting double-strand DNA break repair to influence the irradiated cells’ survival. However, the combination of epigenetic drugs and radiotherapy has only been evaluated in several ongoing clinical trials for limited cancer types, partly due to a lack of knowledge on the potential mechanisms on how radiation induces epigenetic regulation and chromatin remodeling. Here, we review recent advances of radiotherapy and radiotherapy-induced epigenetic remodeling and introduce related technologies for epigenetic monitoring. Particularly, we exploit the application of fluorescence resonance energy transfer (FRET) biosensors to visualize dynamic epigenetic regulations in single living cells and tissue upon radiotherapy and drug treatment. We aim to bridge FRET biosensor, epigenetics, and radiotherapy, providing a perspective of using FRET to assess epigenetics and provide guidance for radiotherapy to improve cancer treatment. In the end, we discuss the feasibility of a combination of epigenetic drugs and radiotherapy as new approaches for cancer therapeutics.
Highlights
Radiotherapy is one of the most effective cancer treatments with a history of more than 100 years
It is understood that when interacting with other particles, secondary electrons deposit their energy by means of inelastic collisions through the ionization and excitation of target molecules
DNA strand breaks (DSB) are, in turn, known to be the most critical damage of the DNA, whose mis-repairing can result in chromosome aberrations, cell death, and carcinogenesis (Figure 1; Lavelle and Foray, 2014; Tang et al, 2019)
Summary
Qin Peng1,2,3*†, Kegui Weng2,3,4†, Shitian Li2,3†, Richard Xu2,3, Yingxiao Wang and Yongzhong Wu4*. DNA break and epigenetic remodeling can be induced by radiotherapy. The combination of epigenetic drugs and radiotherapy has only been evaluated in several ongoing clinical trials for limited cancer types, partly due to a lack of knowledge on the potential mechanisms on how radiation induces epigenetic regulation and chromatin remodeling. We review recent advances of radiotherapy and radiotherapy-induced epigenetic remodeling and introduce related technologies for epigenetic monitoring. We exploit the application of fluorescence resonance energy transfer (FRET) biosensors to visualize dynamic epigenetic regulations in single living cells and tissue upon radiotherapy and drug treatment. We aim to bridge FRET biosensor, epigenetics, and radiotherapy, providing a perspective of using FRET to assess epigenetics and provide guidance for radiotherapy to improve cancer treatment.
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