The effect of iodine-131 beta-particles in combination with A-966492 and Topotecan on radio-sensitization of glioblastoma: An in-vitro study

Koosha, Fereshteh; Eynali, Samira; Eyvazzadeh, Nazila; Kamalabadi, Mahdieh Ahmadi

doi:10.1016/j.apradiso.2021.109904

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…As previously mentioned, PARP is an intracellular protein involved in the repair of single and double-stranded DNA breaks [ 7 , 8 ], and radiotherapy exerts its cytotoxic mitotic effects on tumor cells through DNA damage [ 58 , 59 ], so the combination with a PARP inhibitor would sensitize the effect to DNA-damaging induced by radiation. This sensitizing effect has been demonstrated in in vitro studies for both fraction radiotherapy and continuous LDR radiotherapy [ 60 , 61 , 62 , 63 ]; meanwhile, some clinical studies have investigated it [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

Wei

Guo

et al. 2021

Current Oncology

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Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.

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Section: Discussionmentioning

confidence: 99%

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

Wei

Guo

et al. 2021

Current Oncology

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“…The combination therapy approach has demonstrated effectiveness in overcoming resistance to β-radiotherapy, particularly in glioblastomas that have exhibited resistance to such treatment. To address this challenge, the combination of 131 I in either topoisomerase I, topotecan, or PARA, A-966492, inhibitors led to a significant increase in cell death and γ-H2AX foci in glioblastoma cells [183]. Furthermore, in a mouse model of glioblastoma, the administration of 131 I-PARPi activated p53 expression and significantly prolonged the overall survival of the tumor-bearing mice [184].…”

Section: Combination Of Radiopharmaceuticals and Dna Damage Repair In...mentioning

confidence: 99%

DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair

Khazaei Monfared,

Heidari,

Klempner

et al. 2023

Pharmaceutics

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DNA is an organic molecule that is highly vulnerable to chemical alterations and breaks caused by both internal and external factors. Cells possess complex and advanced mechanisms, including DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which together minimize the potentially harmful effects of DNA damage. However, in cancer cells, the normal DNA damage tolerance and response processes are disrupted or deregulated. This results in increased mutagenesis and genomic instability within the cancer cells, a known driver of cancer progression and therapeutic resistance. On the other hand, the inherent instability of the genome in rapidly dividing cancer cells can be exploited as a tool to kill by imposing DNA damage with radiopharmaceuticals. As the field of targeted radiopharmaceutical therapy (RPT) is rapidly growing in oncology, it is crucial to have a deep understanding of the impact of systemic radiation delivery by radiopharmaceuticals on the DNA of tumors and healthy tissues. The distribution and activation of DNA damage and repair pathways caused by RPT can be different based on the characteristics of the radioisotope and molecular target. Here we provide a comprehensive discussion of the biological effects of RPTs, with the main focus on the role of varying radioisotopes in inducing direct and indirect DNA damage and activating DNA repair pathways.

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“…Additionally, Sefl et al showed that neglecting the initial uptake phase will lead to a substantial overestimation of the absorbed dose, and thus, an underestimation of cell survival [ 78 ]. Nonetheless, 15 out of the 27 studies reporting survival vs. dose (52%) evaluated the RP uptake at only a single time-point and neglected biological decay, which can result in an overestimation of the absorbed dose [ 10 , 14 , 35 , 37 , 38 , 39 , 41 , 66 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ].…”

Section: Preclinical Dosimetrymentioning

confidence: 99%

A Review on Tumor Control Probability (TCP) and Preclinical Dosimetry in Targeted Radionuclide Therapy (TRT)

et al. 2022

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Targeted radionuclide therapy (TRT) uses radiopharmaceuticals to specifically irradiate tumor cells while sparing healthy tissue. Response to this treatment highly depends on the absorbed dose. Tumor control probability (TCP) models aim to predict the tumor response based on the absorbed dose by taking into account the different characteristics of TRT. For instance, TRT employs radiation with a high linear energy transfer (LET), which results in an increased effectiveness. Furthermore, a heterogeneous radiopharmaceutical distribution could result in a heterogeneous dose distribution at a tissue, cellular as well as subcellular level, which will generally reduce the tumor response. Finally, the dose rate in TRT is protracted, relatively low, and variable over time. This allows cells to repair more DNA damage, which may reduce the effectiveness of TRT. Within this review, an overview is given on how these characteristics can be included in TCP models, while some experimental findings are also discussed. Many parameters in TCP models are preclinically determined and TCP models also play a role in the preclinical stage of radiopharmaceutical development; however, this all depends critically on the calculated absorbed dose. Accordingly, an overview of the existing preclinical dosimetry methods is given, together with their limitation and applications. It can be concluded that although the theoretical extension of TCP models from external beam radiotherapy towards TRT has been established quite well, the experimental confirmation is lacking. Thus, requiring additional comprehensive studies at the sub-cellular, cellular, and organ level, which should be provided with accurate preclinical dosimetry.

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The effect of iodine-131 beta-particles in combination with A-966492 and Topotecan on radio-sensitization of glioblastoma: An in-vitro study

Cited by 7 publications

References 26 publications

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair

A Review on Tumor Control Probability (TCP) and Preclinical Dosimetry in Targeted Radionuclide Therapy (TRT)

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