Radiotherapy modulates tumor cell fate decisions: a review

Chen, Haoran; Han, Zhongyu; Luo, Qian; Wang, Yi; Qi-ju, LI; Zhou, Lisui; Zuo, Hou-Dong

doi:10.1186/s13014-022-02171-7

Cited by 35 publications

(18 citation statements)

References 130 publications

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“…Therefore, to find out the downstream molecular markers involved in cell death, a DNA damage marker and a cell death marker were evaluated. H2AX phosphorylation (γH2AX) is a well-known marker of an early cellular response to DNA double-strand breaks, and Caspase 3 is a key molecule involved in cell death ( Chen et al, 2022 ; Widjaja et al, 2023 ). In this study, western blot analysis showed that Bi-212-MAA treatment induced H2AX phosphorylation in 4T1-treated cells ( Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

“…Further, no change was seen in markers of radioresistance, specifically proteins involved in cell cycle checkpoint control. It is known that increased radiation dose can lead to cell cycle arrest and cell survival, making it critical to find a sensitive dose ( Chan Wah Hak et al, 2022 ; Chen et al, 2022 ; Widjaja et al, 2023 ). Alpha (α)-particle therapy works through direct double-stranded DNA breaks, thus leaving the cell with very few options for resistance and survival.…”

Section: Discussionmentioning

confidence: 99%

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Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models

Kauffman

Singh

Morrison³

et al. 2023

Front. Chem.

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Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays in vitro and using immune-competent mouse models of breast cancer. The in vivo biodistribution of Bi-212-MAA was investigated in Balb/c and C57BL/6 mice with 4T1 and EO771 orthotopic breast tumors, respectively. The same orthotopic breast cancer models were used to evaluate the treatment efficacy of Bi-212-MAA. Our results showed that macroaggregated albumin can be stably radiolabeled with Bi-212 and that Bi-212-MAA can deliver significant radiation therapy to reduce the growth and clonogenic potential of 4T1 and EO771 cells in vitro. Additionally, Bi-212-MAA treatment upregulated γH2AX and cleaved Caspase-3 expression in 4T1 cells. Biodistribution analyses showed 87–93% of the Bi-212-MAA remained in 4T1 and EO771 tumors 2 and 4 h after injection. Following single-tumor treatments with Bi-212-MAA there was a significant reduction in the growth of both 4T1 and EO771 breast tumors over the 18-day monitoring period. Overall, these findings showed that Bi-212-MAA was stably radiolabeled and inhibited breast cancer growth. Bi-212-MAA is an exciting platform to study α-particle therapy and will be easily translatable to larger animal models and human clinical trials.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models

Kauffman

Singh

Morrison³

et al. 2023

Front. Chem.

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“…Our results preliminarily suggest that KCTD5 is involved in the regulation of tumor cell apoptosis, but the specific regulatory mechanism remains unclear. Regulation of the apoptosis signaling pathway is an important way to improve cancer therapy [ 27 , 28 ]. KCTD5 may be a potential target for tumor therapy.…”

Section: Discussionmentioning

confidence: 99%

Identifies KCTD5 as a novel cancer biomarker associated with programmed cell death and chemotherapy drug sensitivity

Shi

Yan

et al. 2023

BMC Cancer

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Background More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity. Methods We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells. Results The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs. Conclusion Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis.

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“…Radiotherapy is one of the most widely used conventional therapeutic strategies for cancer patients [ 1 ]. DNA double-strand breaks induced by ionizing radiation are one of the main mechanisms of its antitumor effect [ 2 ]. However, the serious side effects on the human body are a major concern in radiotherapy [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy

Shen,

Wang,

et al. 2024

Bioactive Materials

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Radiotherapy modulates tumor cell fate decisions: a review

Cited by 35 publications

References 130 publications

Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models

Effective therapy with Bismuth-212 labeled macroaggregated albumin in orthotopic mouse breast tumor models

Identifies KCTD5 as a novel cancer biomarker associated with programmed cell death and chemotherapy drug sensitivity

Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy

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