Clinical Progress in Proton Radiotherapy: Biological Unknowns

Vanderwaeren, Laura; Dok, Rüveyda; Verstrepen, Kevin J.; Nuyts, Sandra

doi:10.3390/cancers13040604

Cited by 32 publications

(23 citation statements)

References 121 publications

(87 reference statements)

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“…Successful establishment of a test would help to select patients for clinical trials on strategies to overcome tumor resistance, and to exclude patients with no expected benefit. Several exciting strategies are upcoming, like combination therapy with radiation and targeted radiosensitizers, including inhibitors of the PI3K‐AKT pathway and of cell–matrix interactions [ 57 ], or escalation of the radiation dose within normal‐tissue tolerance by proton therapy [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

miR‐200a/b/‐429 downregulation is a candidate biomarker of tumor radioresistance and independent of hypoxia in locally advanced cervical cancer

et al. 2022

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Many patients with locally advanced cervical cancer experience recurrence within the radiation field after chemoradiotherapy. Biomarkers of tumor radioresistance are required to identify patients in need of intensified treatment. Here, the biomarker potential of miR-200 family members was investigated in this disease. Also, involvement of tumor hypoxia in the radioresistance mechanism was determined, using a previously defined 6gene hypoxia classifier. miR-200 expression was measured in pretreatment tumor biopsies of an explorative cohort (n = 90) and validation cohort 1 (n = 110) by RNA sequencing. Publicly available miR-200 data of 79 patients were included for the validation of prognostic significance. A score based on expression of the miR-200a/b/-429 (miR-200a, miR-200b, and miR-429) cluster showed prognostic significance in all cohorts. The score was significant in multivariate analysis of central pelvic recurrence. No association with distant recurrence or hypoxia status was found. Potential miRNA target genes were identified from gene expression profiles and showed enrichment of genes in extracellular matrix organization and cell adhesion. miR-200a/b/-429 overexpression had a pronounced radiosensitizing effect in tumor xenografts, whereas the effect was minor in vitro. In conclusion, miR-200a/b/-429 downregulation is a candidate biomarker of central pelvic recurrence and seems to predict cell adhesion-mediated tumor radioresistance independent of clinical markers and hypoxia.

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Section: Discussionmentioning

confidence: 99%

miR‐200a/b/‐429 downregulation is a candidate biomarker of tumor radioresistance and independent of hypoxia in locally advanced cervical cancer

et al. 2022

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“…Higher-LET values do exist across the track of the proton beam particularly towards the distal edge of the spread-out Bragg peak (SOBP), compared with conventional X-ray radiation (Ref. 21). This radiation modality allows for a better distribution of the delivered dose of radiation compared to photon (X-Ray) radiotherapy and has led to an expansion of the treatment options in radiation oncology.…”

Section: Overview Of Medium To High-let Radiotherapies (Protons Neutr...mentioning

confidence: 99%

Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair

Nikitaki

Velalopoulou

Zanni

et al. 2022

Expert Rev. Mol. Med.

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DNA damage and repair studies are at the core of the radiation biology field and represent also the fundamental principles informing radiation therapy (RT). DNA damage levels are a function of radiation dose, whereas the type of damage and biological effects such as DNA damage complexity, depend on radiation quality that is linear energy transfer (LET). Both levels and types of DNA damage determine cell fate, which can include necrosis, apoptosis, senescence or autophagy. Herein, we present an overview of current RT modalities in the light of DNA damage and repair with emphasis on medium to high-LET radiation. Proton radiation is discussed along with its new adaptation of FLASH RT. RT based on α-particles includes brachytherapy and nuclear-RT, that is proton-boron capture therapy (PBCT) and boron-neutron capture therapy (BNCT). We also discuss carbon ion therapy along with combinatorial immune-based therapies and high-LET RT. For each RT modality, we summarise relevant DNA damage studies. Finally, we provide an update of the role of DNA repair in high-LET RT and we explore the biological responses triggered by differential LET and dose.

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“…Radiation-based anticancer therapies, such as X-ray-, gamma ray-, proton- or boron neutron capture therapy, are used for the local treatment of tumors [ 5 , 6 , 7 ]. The use of individual radiotherapy mode depends, among others, on the location of cancer.…”

Section: Introductionmentioning

confidence: 99%

Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures

Klębowski

Stec

Depciuch

et al. 2022

Cancers

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Nano-sized radiosensitizers can be used to increase the effectiveness of radiation-based anticancer therapies. In this study, bimetallic, ⁓30 nm palladium-platinum nanoparticles (PdPt NPs) with different nanostructures (random nano-alloy NPs and ordered core-shell NPs) were prepared. Scanning transmission electron microscopy (STEM), selected area electron diffraction (SAED), energy-dispersive X-ray spectroscopy (EDS), zeta potential measurements, and nanoparticle tracking analysis (NTA) were used to provide the physicochemical characteristics of PdPt NPs. Then, PdPt NPs were added to the cultures of colon cancer cells and normal colon epithelium cells in individually established non-toxic concentrations and irradiated with the non-harmful dose of X-rays/protons. Cell viability before and after PdPt NPs-(non) assisted X-ray/proton irradiation was evaluated by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Flow cytometry was used to assess cell apoptosis. The results showed that PdPt NPs significantly enhanced the effect of irradiation on cancer cells. It was noticed that nano-alloy PdPt NPs possess better radiosensitizing properties compared to PtPd core-shell NPs, and the combined effect against cancer cells was c.a. 10% stronger for X-ray than for proton irradiation. Thus, the radio-enhancing features of differently structured PdPt NPs indicate their potential application for the improvement of the effectiveness of radiation-based anticancer therapies.

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Clinical Progress in Proton Radiotherapy: Biological Unknowns

Cited by 32 publications

References 121 publications

miR‐200a/b/‐429 downregulation is a candidate biomarker of tumor radioresistance and independent of hypoxia in locally advanced cervical cancer

miR‐200a/b/‐429 downregulation is a candidate biomarker of tumor radioresistance and independent of hypoxia in locally advanced cervical cancer

Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair

Improving the Effect of Cancer Cells Irradiation with X-rays and High-Energy Protons Using Bimetallic Palladium-Platinum Nanoparticles with Various Nanostructures

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