Abstract
Proton beam therapy (PBT) offers significant benefit over conventional (photon) radiotherapy for the treatment of a number of different human cancers, largely due to the physical characteristics. In particular, the low entrance dose and maximum energy deposition in depth at a well-defined region, the Bragg peak, can spare irradiation of proximal healthy tissues and organs at risk when compared to conventional radiotherapy using high-energy photons. However, there are still biological uncertainties reflected in the relative biological effectiveness that varies along the track of the proton beam as a consequence of the increases in linear energy transfer (LET). Furthermore, the spectrum of DNA damage induced by protons, particularly the generation of complex DNA damage (CDD) at high-LET regions of the distal edge of the Bragg peak, and the specific DNA repair pathways dependent on their repair are not entirely understood. This knowledge is essential in understanding the biological impact of protons on tumor cells, and ultimately in devising optimal therapeutic strategies employing PBT for greater clinical impact and patient benefit. Here, we provide an up-to-date review on the radiobiological effects of PBT versus photon radiotherapy in cells, particularly in the context of DNA damage. We also review the DNA repair pathways that are essential in the cellular response to PBT, with a specific focus on the signaling and processing of CDD induced by high-LET protons.
Highlights
Since its first application in the 1950s, proton beam therapy (PBT) is gaining ground in radiation oncology thanks to its radiobiological and physical advantages over photon radiotherapy [1]
We provide the latest knowledge of the radiobiology of PBT, in the the areas where ongoing research is necessary, which will have a major impact on the effective clinical context of DNA damage and the repair pathways that are important for the cellular DNA damage response (DDR), and discuss use of PBT for cancer treatment
We recently reported for the first time that monoubiquitylation of lysine 120 on histone H2B is promoted in HeLa and head and neck squamous cell carcinoma (HNSCC) cells in response to complex DNA damage (CDD) induced by low-energy (11 MeV mean energy incident on the cells) protons at the distal edge of an spread-out Bragg peak (SOBP), catalyzed by the E3 ubiquitin ligases ring finger 20/40 complex (RNF20/40) and male-specific lethal 2 homolog (MSL2) [37]
Summary
Since its first application in the 1950s, proton beam therapy (PBT) is gaining ground in radiation oncology thanks to its radiobiological and physical advantages over photon radiotherapy [1]. The cellular DNA damage response (DDR) and repair pathways that are required distal edge of the Bragg peak. The cellular DNA damage response (DDR) and repair for resolving CDD generated by PBT are not fully understood. Related to cancers will display inherent differences in radiosensitivity to PBT, of which proteins this, individual human cancers will display inherent differences in radiosensitivity to involved in the DDR play such an important role. We provide the latest knowledge of the radiobiology of PBT, in the the areas where ongoing research is necessary, which will have a major impact on the effective clinical context of DNA damage and the repair pathways that are important for the cellular DDR, and discuss use of PBT for cancer treatment. PBT to photon radiotherapy, as is Transfer it the ratio of the reference radiation
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