Radiotherapy-Induced Senescence and its Effects on Responses to Treatment

Tabasso, Antonella F S; Jones, Donald J. L.; Jones, George D.D.; Macip, Salvador

doi:10.1016/j.clon.2019.02.003

Cited by 34 publications

(33 citation statements)

References 86 publications

(97 reference statements)

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“…Enhanced p21 waf1 expression can arrest the cell cycle both at G1 and G2 phases to prevent damaged DNA to be duplicated or cells with DNA damages to enter mitosis and let DNA repair mechanisms be recruited [ 65 ]. Permanent p21 waf1 upregulation and cell cycle arrest is called senescence, which may show transitional therapeutic benefits, but hinders radiation-induced tumor destruction [ 66 ]. Moreover, incomplete senescence is thought to be used by tumors as an adaptive pathway to delay but restart proliferation and become more aggressive [ 67 ].…”

Section: Meht-induced Dna Double-strand Breaks and P21 Wmentioning

confidence: 99%

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Krenács

Meggyesházi

Forika

et al. 2020

IJMS

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The benefits of high-fever range hyperthermia have been utilized in medicine from the Ancient Greek culture to the present day. Amplitude-modulated electro-hyperthermia, induced by a 13.56 MHz radiofrequency current (mEHT, or Oncothermia), has been an emerging means of delivering loco-regional clinical hyperthermia as a complementary of radiation-, chemo-, and molecular targeted oncotherapy. This unique treatment exploits the metabolic shift in cancer, resulting in elevated oxidative glycolysis (Warburg effect), ion concentration, and electric conductivity. These promote the enrichment of electric fields and induce heat (controlled at 42 °C), as well as ion fluxes and disequilibrium through tumor cell membrane channels. By now, accumulating preclinical studies using in vitro and in vivo models of different cancer types have revealed details of the mechanism and molecular background of the oncoreductive effects of mEHT monotherapy. These include the induction of DNA double-strand breaks, irreversible heath and cell stress, and programmed cells death; the upregulation of molecular chaperones and damage (DAMP) signaling, which may contribute to a secondary immunogenic tumor cell death. In combination therapies, mEHT proved to be a good chemosensitizer through increasing drug uptake and tumor reductive effects, as well as a good radiosensitizer by downregulating hypoxia-related target genes. Recently, immune stimulation or intratumoral antigen-presenting dendritic cell injection have been able to extend the impact of local mEHT into a systemic “abscopal” effect. The complex network of pathways emerging from the published mEHT experiments has not been overviewed and arranged yet into a framework to reveal links between the pieces of the “puzzle”. In this paper, we review the mEHT-related damage mechanisms published in tumor models, which may allow some geno-/phenotype treatment efficiency correlations to be exploited both in further research and for more rational clinical treatment planning when mEHT is involved in combination therapies.

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Section: Meht-induced Dna Double-strand Breaks and P21 Wmentioning

confidence: 99%

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Krenács

Meggyesházi

Forika

et al. 2020

IJMS

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“…Changes observed in senescent cells include the activation of the tumor suppressor network, morphological changes, altered chromatin structure and an altered spectrum of secreted factors [ 7 , 8 ]. Cancer therapy and especially radiochemotherapy usually causes senescence [ 9 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

Gottwald

Putz

Hohmann

et al. 2020

BMC Mol and Cell Biol

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Background Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

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“…As of 2018, cancer has become the leading cause of death in the U.S. and developed countries 1 . Cancers are relentless when in the brain.…”

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confidence: 99%

Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

Hainfeld

Ridwan

Stanishevskiy

et al. 2020

Sci Rep

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About 30% of breast cancers metastasize to the brain; those widely disseminated are fatal typically in 3–4 months, even with the best available treatments, including surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight, with uptake peaks at 4.5%. This is calculated to provide a dose enhancement factor of approximately 5.5 (peaks at 8.0), the highest ever reported for any radiation-enhancing agents. With RT alone (15 Gy, single dose), all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days.

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Radiotherapy-Induced Senescence and its Effects on Responses to Treatment

Cited by 34 publications

References 86 publications

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Modulated Electro-Hyperthermia-Induced Tumor Damage Mechanisms Revealed in Cancer Models

Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

Iodine nanoparticle radiotherapy of human breast cancer growing in the brains of athymic mice

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