The Regulatory Mechanisms of Dynamin-Related Protein 1 in Tumor Development and Therapy

Han, Ping; Ren, Xinlu; Qu, Xiuxia; Meng, Yiteng

doi:10.1089/cbr.2020.3791

Cited by 2 publications

(3 citation statements)

References 74 publications

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“…Dysregulation of mitochondrial dynamics is often linked to cancer tumourigenesis and progression, as reviewed comprehensively elsewhere [70,71]. Specifically, the upregulation of mitochondrial Drp1 with concomitant downregulation of Mfn2 has been shown to promote tumourigenesis in many cancers including lung, gastric, breast, glioma, colon, ovarian, pancreatic and melanoma [72].…”

Section: The Role Of Drp1 In Cancermentioning

confidence: 99%

“…Current pre-clinical animal and cell culture studies have suggested that Drp1 inhibition is a promising approach for protecting the heart against doxorubicin-induced injury without compromising the anti-cancer properties of doxorubicin in treating various types of cancer. Moreover, Drp1 inhibition appears to exert anti-cancer effects in some cancer cells [70,71] and might also have synergistic anti-cancer effects with doxorubicin and other chemotherapeutic agents in cancers where dysregulation of mitochondrial dynamics occurs; however, this remains to be determined.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology

et al. 2022

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Purpose of Review This study is aimed at reviewing the recent progress in Drp1 inhibition as a novel approach for reducing doxorubicin-induced cardiotoxicity and for improving cancer treatment. Recent Findings Anthracyclines (e.g. doxorubicin) are one of the most common and effective chemotherapeutic agents to treat a variety of cancers. However, the clinical usage of doxorubicin has been hampered by its severe cardiotoxic side effects leading to heart failure. Mitochondrial dysfunction is one of the major aetiologies of doxorubicin-induced cardiotoxicity. The morphology of mitochondria is highly dynamic, governed by two opposing processes known as fusion and fission, collectively known as mitochondrial dynamics. An imbalance in mitochondrial dynamics is often reported in tumourigenesis which can lead to adaptive and acquired resistance to chemotherapy. Drp1 is a key mitochondrial fission regulator, and emerging evidence has demonstrated that Drp1-mediated mitochondrial fission is upregulated in both cancer cells to their survival advantage and injured heart tissue in the setting of doxorubicin-induced cardiotoxicity. Summary Effective treatment to prevent and mitigate doxorubicin-induced cardiotoxicity is currently not available. Recent advances in cardio-oncology have highlighted that Drp1 inhibition holds great potential as a targeted mitochondrial therapy for doxorubicin-induced cardiotoxicity.

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Section: The Role Of Drp1 In Cancermentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology

et al. 2022

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“…Some Drp1 inhibitors have shown significant effects in PAH preclinical and clinical trials, such as restoring mitochondrial function and inhibiting the PAH development ( Parra et al, 2017 ; Tian et al, 2018 ; Zhuan et al, 2020 ; Wu et al, 2021 ). Presently, however, Drp1 inhibitors are mostly discussed in the context of cancer and nervous system disorders, with little clinical research on PAH ( Reddy, 2014 ; Han et al, 2021 ; Dhapola et al, 2022 ). This review seeks to shed more light on clinical therapy for PAH and to provide novel points.…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of Mitochondrial Dynamics Mediated by Dynamin-Related Protein 1 in Pulmonary Arterial Hypertension

Xiao

Zhang

Wang

2022

Front. Cell Dev. Biol.

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Pulmonary arterial hypertension (PAH) is a chronic, lethal pulmonary disease characterized by pulmonary vascular remodeling. It leads to malignant results, such as rupture of pulmonary arterial dissection, dyspnea, right heart failure, and even death. Previous studies have confirmed that one of the main pathological changes of this disease is abnormal mitochondrial dynamics, which include mitochondrial fission, fusion, and autophagy that keep a dynamic balance under certain physiological state. Dynamin-related protein 1 (Drp1), the key molecule in mitochondrial fission, mediates mitochondrial fission while also affecting mitochondrial fusion and autophagy through numerous pathways. There are various abnormalities of Drp1 in PAH pathophysiology, including Drp1 overexpression and activation as well as an upregulation of its outer mitochondrial membrane ligands. These aberrant alterations will eventually induce the development of PAH. With the process of recent studies, the structure and function of Drp1 have been gradually revealed. Meanwhile, inhibitors targeting this pathway have also been discovered. This review aims to shed more light on the mechanism of Drp1 and its inhibitors in the abnormal mitochondrial dynamics of PAH. Furthermore, it seeks to provide more novel insights to clinical therapy.

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The Regulatory Mechanisms of Dynamin-Related Protein 1 in Tumor Development and Therapy

Cited by 2 publications

References 74 publications

Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology

Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology

Inhibitors of Mitochondrial Dynamics Mediated by Dynamin-Related Protein 1 in Pulmonary Arterial Hypertension

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