International Journal of Molecular Sciences

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New Insights into Radiation Oncology

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Dear Colleagues,

The Special Issue “New Insights into Radiation Oncology” covers all aspects of research affecting the treatment of cancer using radiation. It publishes findings from molecular and cellular radiobiology, radiation physics, radiation technology, and clinical oncology.

In addition to surgical removal and chemotherapy, radiotherapy plays an important role in numerous tumor entities. Particle irradiation with protons and carbon ions is particularly indicated for therapy-resistant tumor types such as sarcomas and chordomas, where conventional photon therapy (X-ray radiation) does not achieve satisfactory results. There are still many outstanding issues, particularly in the area of basic research.

Dr. Birgit Lohberger
Guest Editor

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Research

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16 pages, 7106 KiB

Open AccessArticle

DNA-PKcs Inhibition Sensitizes Human Chondrosarcoma Cells to Carbon Ion Irradiation via Cell Cycle Arrest and Telomere Capping Disruption

by Birgit Lohberger, Sandra Barna, Dietmar Glänzer, Nicole Eck, Andreas Leithner and Dietmar Georg

Int. J. Mol. Sci. 2024, 25(11), 6179; https://doi.org/10.3390/ijms25116179 - 4 Jun 2024

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Abstract

In order to overcome the resistance to radiotherapy in human chondrosarcoma cells, the prevention from efficient DNA repair with a combined treatment with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitor AZD7648 was explored for carbon ion (C-ion) as well as reference photon (X-ray) irradiation (IR) using gene expression analysis, flow cytometry, protein phosphorylation, and telomere length shortening. Proliferation markers and cell cycle distribution changed significantly after combined treatment, revealing a prominent G₂/M arrest. The expression of the G₂/M checkpoint genes cyclin B, CDK1, and WEE1 was significantly reduced by IR alone and the combined treatment. While IR alone showed no effects, additional AZD7648 treatment resulted in a dose-dependent reduction in AKT phosphorylation and an increase in Chk2 phosphorylation. Twenty-four hours after IR, the key genes of DNA repair mechanisms were reduced by the combined treatment, which led to impaired DNA repair and increased radiosensitivity. A time-dependent shortening of telomere length was observed in both cell lines after combined treatment with AZD7648 and 8 Gy X-ray/C-ion IR. Our data suggest that the inhibition of DNA-PKcs may increase sensitivity to X-rays and C-ion IR by impairing its functional role in DNA repair mechanisms and telomere end protection. Full article

(This article belongs to the Special Issue New Insights into Radiation Oncology)

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45 pages, 1174 KiB

Open AccessReview

Proton Radiation Therapy: A Systematic Review of Treatment-Related Side Effects and Toxicities

by Peter P. Salem, Perla Chami, Remy Daou, Joseph Hajj, Haibo Lin, Arpit M. Chhabra, Charles B. Simone II, Nancy Y. Lee and Carla Hajj

Int. J. Mol. Sci. 2024, 25(20), 10969; https://doi.org/10.3390/ijms252010969 - 11 Oct 2024

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Abstract

Cancer is the second leading cause of death worldwide. Around half of all cancer patients undergo some type of radiation therapy throughout the course of their treatment. Photon radiation remains (RT) the most widely utilized modality of radiotherapy despite recent advancements in proton radiation therapy (PBT). PBT makes use of the particle’s biological property known as the Bragg peak to better spare healthy tissue from radiation damage, with data to support that this treatment modality is less toxic than photon RT. Hence, proton radiation dosimetry looks better compared to photon dosimetry; however, due to proton-specific uncertainties, unexpected acute, subacute, and long-term toxicities can be encountered. Reported neurotoxicity resulting from proton radiation treatments include radiation necrosis, moyamoya syndrome, neurosensory toxicities, brain edema, neuromuscular toxicities, and neurocognitive toxicities. Pulmonary toxicities include pneumonitis and fibrosis, pleural effusions, and bronchial toxicities. Pericarditis, pericardial effusions, and atrial fibrillations are among the cardiac toxicities related to proton therapy. Gastrointestinal and hematological toxicities are also found in the literature. Genitourinary toxicities include urinary and reproductive-related toxicities. Osteological, oral, endocrine, and skin toxicities have also been reported. The side effects will be comparable to the ones following photon RT, nonetheless at an expected lower incidence. The toxicities collected mainly from case reports and clinical trials are described based on the organs affected and functions altered. Full article

(This article belongs to the Special Issue New Insights into Radiation Oncology)

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