Heavy charged particle radiobiology: Using enhanced biological effectiveness and improved beam focusing to advance cancer therapy

Allen, Chris; Borak, Thomas B.; Tsujii, Hirohiko; Nickoloff, Jac A.

doi:10.1016/j.mrfmmm.2011.02.012

Cited by 80 publications

(58 citation statements)

References 66 publications

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“…This is why X-rays and γ-rays are considered sparsely ionizing, or low-linear energy transfer (LET), forms of IR. On the other hand, particulate forms of ionizing radiation such as neutrons, α particles, or carbon ions, are considered densely ionizing, or high LET, forms of radiation because they ionize along their tracks at a higher rate than the electrons generated by X-rays (64). …”

Section: Systematic Analysis Of Dsb Complexity Levelsmentioning

confidence: 99%

DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice

Schipler

Iliakis

2013

Nucleic Acids Research

245

232

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Although the DNA double-strand break (DSB) is defined as a rupture in the double-stranded DNA molecule that can occur without chemical modification in any of the constituent building blocks, it is recognized that this form is restricted to enzyme-induced DSBs. DSBs generated by physical or chemical agents can include at the break site a spectrum of base alterations (lesions). The nature and number of such chemical alterations define the complexity of the DSB and are considered putative determinants for repair pathway choice and the probability that errors will occur during this processing. As the pathways engaged in DSB processing show distinct and frequently inherent propensities for errors, pathway choice also defines the error-levels cells opt to accept. Here, we present a classification of DSBs on the basis of increasing complexity and discuss how complexity may affect processing, as well as how it may cause lethal or carcinogenic processing errors. By critically analyzing the characteristics of DSB repair pathways, we suggest that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis. In the same framework, we also analyze the rational of DSB repair pathway choice.

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Section: Systematic Analysis Of Dsb Complexity Levelsmentioning

confidence: 99%

DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice

Schipler

Iliakis

2013

Nucleic Acids Research

245

232

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“…Thus, it is estimated that while the RBE for protons could vary from 1.02 at the proximal edge to 1.4 at the distal edge, the corresponding RBE for 12 C ions could range from 1.5 at proximal edge to 6.7 at the distal edge [33]. The average RBE for 12 C is therefore considered to vary between 2.5 and 3 [34]. Although physically both protons and 12 C could reasonably conform to the dose distribution around the tumour, a RBE difference of two to three times in favour of 12 C could be translated into a higher differential tumour cell kill.…”

Section: Particle Beam Therapy: Protons and Carbonsmentioning

confidence: 99%

Could hyperthermia with proton therapy mimic carbon ion therapy? Exploring a thermo-radiobiological rationale

Datta

Puric

Schneider

et al. 2014

International Journal of Hyperthermia

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Hyperthermia has been conventionally used in conjunction with photon beam irradiation. With a gradual increase in particle therapy facilities worldwide, this paper explores the physical, thermal and radiobiological implications of using a combination of hyperthermia with proton beam therapy. Hyperthermia is known to exhibit radiobiological features similar to those of high linear energy transfer radiation. Protons have many of the physical dose distribution properties of (12)C ion therapy. Thus, the thermo-radiobiological advantages of hyperthermia coupled with the physical dose distribution advantages of proton beams could possibly mimic (12)C ion therapy.

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“…Radiotherapy using carbon ions has received great attention because it offers improved tumor targeting and increased biological effectiveness (13, 14). Unlike low LET radiation, high LET radiation such as carbon ions overcomes radio-resistance of S-phase and hypoxic cells (15, 16), and it induces more complex DSBs that are repaired more slowly than X-ray induced DSBs (14, 17).…”

Section: Introductionmentioning

confidence: 99%

TAS-116, a Novel Hsp90 Inhibitor, Selectively Enhances Radiosensitivity of Human Cancer Cells to X-rays and Carbon Ion Radiation

Lee¹,

Sunada

Hirakawa³

et al. 2017

Molecular Cancer Therapeutics

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Hsp90 inhibitors have been investigated as cancer therapeutics in mono-therapy and to augment radiotherapy, however serious adverse effects of early generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here we investigated the radio-sensitizing effects of TAS-116 in low LET X-ray, and high LET carbon ion irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of non-cancerous human fibroblasts. TAS-116 increased the number of radiation-induced γ-H2AX foci, and delayed the repair of DNA double-strand breaks (DSBs). TAS-116 reduced the expression of proteins that mediate repair of DSBs by homologous recombination (RAD51) and non-homologous end joining (Ku, DNA-PKcs), and suppressed formation of RAD51 foci and phosphorylation/activation of DNA-PKcs. TAS-116 also decreased expression of the cdc25 cell cycle progression marker, markedly increasing G2/M arrest. Combined treatment of mouse tumor xenografts with carbon ions and TAS-116 showed promising delay in tumor growth compared to either individual treatment. These results demonstrate that TAS-116 radio-sensitizes human cancer cells to both X rays and carbon ions by inhibiting the two major DSB repair pathways, and these effects were accompanied by marked cell cycle arrest. The promising results of combination TAS-116 + carbon ion radiation therapy of tumor xenografts justify further exploration of TAS-116 as an adjunct to radiotherapy using low or high LET radiation.

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Heavy charged particle radiobiology: Using enhanced biological effectiveness and improved beam focusing to advance cancer therapy

Cited by 80 publications

References 66 publications

DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice

DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice

Could hyperthermia with proton therapy mimic carbon ion therapy? Exploring a thermo-radiobiological rationale

TAS-116, a Novel Hsp90 Inhibitor, Selectively Enhances Radiosensitivity of Human Cancer Cells to X-rays and Carbon Ion Radiation

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