Targeting the heat shock response in combination with radiotherapy: Sensitizing cancer cells to irradiation-induced cell death and heating up their immunogenicity

Lauber, Kirsten; Brix, Nikko; Ernst, Anne; Hennel, Roman; Krombach, Julia; Anders, Heike; Belka, Claus

doi:10.1016/j.canlet.2015.02.047

Cited by 58 publications

(63 citation statements)

References 277 publications

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“…However, these pathways are affected to different extents by HSP90 inhibition, and quantitative phospho-proteome analyses have identified proteins involved in the DDR and protein kinases to be the most susceptible ones [28,29]. Therefore, we decided to choose a low concentration of NW457, which per se did only marginally affect cellular viability, for the combination experiments with ionizing irradiation.…”

Section: Viability Of Soft Tissue Sarcoma Cell Lines Is Differentiallmentioning

confidence: 98%

HSP90 inhibition as a means of radiosensitizing resistant, aggressive soft tissue sarcomas

et al. 2015

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Section: Viability Of Soft Tissue Sarcoma Cell Lines Is Differentiallmentioning

confidence: 98%

HSP90 inhibition as a means of radiosensitizing resistant, aggressive soft tissue sarcomas

et al. 2015

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“…The combination of hyperthermia and proton therapy [78] can also easily be incorporated. Immune response is also known to be triggered by RT and by HT [79]. Inclusion of this phenomenon in TRTP is worthwhile but challenging, as this effect also depends strongly on combination with other agents, and more research is needed to provide the dosimetry data needed for incorporation in TRTP.…”

Section: Future Prospects and Perspectivementioning

confidence: 99%

Thermoradiotherapy planning: Integration in routine clinical practice

Crezee

Leeuwen

Oei

et al. 2015

International Journal of Hyperthermia

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Planning of combined radiotherapy and hyperthermia treatments should be performed taking the synergistic action between the two modalities into account. This work evaluates the available experimental data on cytotoxicity of combined radiotherapy and hyperthermia treatment and the requirements for integration of hyperthermia and radiotherapy treatment planning into a single planning platform. The underlying synergistic mechanisms of hyperthermia include inhibiting DNA repair, selective killing of radioresistant hypoxic tumour tissue and increased radiosensitivity by enhanced tissue perfusion. Each of these mechanisms displays different dose-effect relations, different optimal time intervals and different optimal sequences between radiotherapy and hyperthermia. Radiosensitisation can be modelled using the linear-quadratic (LQ) model to account for DNA repair inhibition by hyperthermia. In a recent study, an LQ model-based thermoradiotherapy planning (TRTP) system was used to demonstrate that dose escalation by hyperthermia is equivalent to $10 Gy for prostate cancer patients treated with radiotherapy. The first step for more reliable TRTP is further expansion of the data set of LQ parameters for normally oxygenated normal and tumour tissue valid over the temperature range used clinically and for the relevant time intervals between radiotherapy and hyperthermia. The next step is to model the effect of hyperthermia in hypoxic tumour cells including the physiological response to hyperthermia and the resulting reoxygenation. Thermoradiotherapy planning is feasible and a necessity for an optimal clinical application of hyperthermia combined with radiotherapy in individual patients.

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“…Treatments of cancer patients by using hyperthermia and stimulating their immune system have always been closely intertwined, as can be exemplified by the fact that William B. Coley is regarded as one of the fathers in the hyperthermia field, but is also seen as one of the pioneers in immunotherapy [6,69]. The many intriguing ways in which hyperthermia stimulates the immune system has great impact on the rationale of hyperthermia treatment in oncology, as is clear from the many reviews on the subject [5,[69][70][71][72][73]. Currently, it is thought that there are two closely related ways in which local hyperthermia can modulate the immune system [5].…”

Section: The Immune System and Hyperthermiamentioning

confidence: 99%

“…Increased temperatures affect both adaptive and innate immunity [70,73]. The way temperature regulates the immune system is not only dependent on the magnitude of the temperature increase that is applied or achieved, but also on the duration [70,72,74].…”

Section: The Immune System and Hyperthermiamentioning

confidence: 99%

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

Tempel¹,

Horsman

Kanaar³

2016

International Journal of Hyperthermia

101

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It has long been established that hyperthermia increases the therapeutic benefit of radiation and chemotherapy in cancer treatment. During the last few years there have been substantial technical improvements in the sources used to apply and measure heat, which greatly increases enthusiasm for the clinical use of hyperthermia. These advances are converging with a better understanding of the physiological and molecular effects of hyperthermia. Therefore, we are now at a juncture where the parameters that will influence the efficacy of hyperthermia in cancer treatment can be optimised in a more systematic and rational manner. In addition, the novel insights in hyperthermia's many biological effects on tumour cells will ultimately result in new treatment regimes. For example, the molecular effects of hyperthermia on the essential cellular process of DNA repair suggest novel combination therapies, with DNA damage response targeting drugs that should now be clinically explored. Here, we provide an overview of recent studies on the various macroscopic and microscopic biological effects of hyperthermia. We indicate the significance of these effects on current treatments and suggest how they will help design novel future treatments. ARTICLE HISTORY

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Targeting the heat shock response in combination with radiotherapy: Sensitizing cancer cells to irradiation-induced cell death and heating up their immunogenicity

Cited by 58 publications

References 277 publications

HSP90 inhibition as a means of radiosensitizing resistant, aggressive soft tissue sarcomas

HSP90 inhibition as a means of radiosensitizing resistant, aggressive soft tissue sarcomas

Thermoradiotherapy planning: Integration in routine clinical practice

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

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