Sorafenib blocks the activation of the HIF-2α/VEGFA/EphA2 pathway, and inhibits the rapid growth of residual liver cancer following high-intensity focused ultrasound therapy in vivo

Wu, Lun; Zhou, Jiao; Zhou, Wenbo; Huang, Xuefei; Chen, Qinhua; Wang, Wei; Zhai, Limin; Li, Shengwei; Tang, Zhigang

doi:10.1016/j.prp.2020.153270

Cited by 10 publications

(14 citation statements)

References 30 publications

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“…Two other studies conducted by Wu et al (2017) ; Wu et al (2021) also demonstrated that overexpression of EphA2, VEGFA, and HIF-2α were closely associated with angiogenesis in residual HCC after HIFU ablation. Moreover, the expression of EphA2, VEGFA, and HIF-2α could be significantly inhibited by sorafenib ( Wu et al, 2021 ). Thus, inhibiting HIF-1, 2α alone or in combination with angiogenesis inhibitors might prevent residual recurrence of HCC after HIFU ablation.…”

Section: The Roles Of Hif and The Related Signaling Pathway In Hcc Af...mentioning

confidence: 80%

“…Therefore, the authors suggested HIFU ablation might result in the hypoxia condition of residual tumor and induce tumor angiogenesis via HIF-1, 2α/VEGFA/EphA2 (Wu et al, 2014). Two other studies conducted by Wu et al (2017); Wu et al (2021) also demonstrated that overexpression of EphA2, VEGFA, and HIF-2α were closely associated with angiogenesis in residual HCC after HIFU ablation. Moreover, the expression of EphA2, VEGFA, and HIF-2α could be significantly inhibited by sorafenib (Wu et al, 2021).…”

Section: Clinical Implications Of Hif-1α In Hcc After Ablationmentioning

confidence: 96%

“…The combination of current sorafenib treatment with gene therapy or inhibitors against HIFs has been documented as promising approach to overcome sorafenib resistance both in vitro and in vivo . Wu et al (2021) reported that the synergistic effect of the combination of HIFU with sorafenib therapy inhibited HCC tumor growth when compared with HIFU treatment alone or with no treatment, which was closely related to the decreased HIF-2α, VEGFA. Gong et al (2017) also found that sorafenib in combination with RFA significantly improved the outcomes of early small HCC, which might be associated with decreased serum levels of active tumor growth factors HIF-1α.…”

Section: Combination Therapies In the Management Of Early And Unresec...mentioning

confidence: 99%

“… Mu et al (2021) found that HIF-2α knockdown decreased the expression of downstream c-MYC, suppressed hypoxic cell proliferation, and induced HCC cell apoptosis, whereas HIF-1α knockdown did not. Wu et al the expression of HIF-2α can be inhibited by sorafenib, which is likely to provide an effective adjunct treatment for patients with HCC following HIFU ablation ( Wu et al, 2021 ).…”

Section: Roles Of Hif Inhibitors For the Treatment Of Hcc And Its Pro...mentioning

confidence: 99%

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Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Xiao

Liu

et al. 2023

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.

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Section: The Roles Of Hif and The Related Signaling Pathway In Hcc Af...mentioning

confidence: 80%

Section: Clinical Implications Of Hif-1α In Hcc After Ablationmentioning

confidence: 96%

Section: Combination Therapies In the Management Of Early And Unresec...mentioning

confidence: 99%

Section: Roles Of Hif Inhibitors For the Treatment Of Hcc And Its Pro...mentioning

confidence: 99%

See 2 more Smart Citations

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Xiao

Liu

et al. 2023

Front. Pharmacol.

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“…Based on the obtained results, considering the overall behaviour, SLN A8-DB was selected for the encapsulation of SRF, a drug approved for the treatment of kidney cancer and advanced liver cancer [44][45][46][47][48][49][50] that has been recently investigated for the potential treatment of uveal melanoma and retinal neovascular diseases [2,3,7,8,11,[51][52][53].…”

Section: In Vitro Characterisationmentioning

confidence: 99%

Sorafenib Repurposing for Ophthalmic Delivery by Lipid Nanoparticles: A Preliminary Study

Bonaccorso

Pepe²,

Zappulla³

et al. 2021

Pharmaceutics

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Uveal melanoma is the second most common melanoma and the most common intraocular malignant tumour of the eye. Among various treatments currently studied, Sorafenib was also proposed as a promising drug, often administered with other compounds in order to avoid resistance mechanisms. Despite its promising cellular activities, the use of Sorafenib by oral administration is limited by its severe side effects and the difficulty to reach the target. The encapsulation into drug delivery systems represents an interesting strategy to overcome these limits. In this study, different lipid nanoparticulate formulations were prepared and compared in order to select the most suitable for the encapsulation of Sorafenib. In particular, two solid lipids (Softisan or Suppocire) at different concentrations were used to produce solid lipid nanoparticles, demonstrating that higher amounts were able to achieve smaller particle sizes, higher homogeneity, and longer physical stability. The selected formulations, which demonstrated to be biocompatible on Statens Seruminstitut Rabbit Cornea cells, were modified to improve their mucoadhesion, evaluating the effect of two monovalent cationic lipids with two lipophilic chains. Sorafenib encapsulation allowed obtaining a sustained and prolonged drug release, thus confirming the potential use of the developed strategy to topically administer Sorafenib in the treatment of uveal melanoma.

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Metal‐Organic Framework‐Mediated Synergistic Hypoxia‐Activated Chemo‐Immunotherapy Induced by High Intensity Focused Ultrasound for Enhanced Cancer Theranostics

Sun,

Li,

Zhou

et al. 2023

Small

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High intensity focused ultrasound (HIFU) has attracted considerable attention as a noninvasive, efficient, and economic therapeutic modality for solid tumors. However, HIFU surgery has its intrinsic limitation in completely ablating tumors, leading to residual tumor tissue. Furthermore, the severely hypoxic environment ensuring after surgery can exacerbate the unrestricted proliferation and metabolism of residual tumor cells, leading to tumor recurrence and metastasis. To address these limitations, a versatile HIFU‐specific metal‐organic framework nanosystem (called ADMOFs) is developed by coordinating hypoxia‐activated prodrug AQ4N, Mn2+, and DOX based on the postoperative response to changes in the tumor microenvironment. ADMOFs loaded with AQ4N/Mn2+ exhibited remarkable tumor‐targeting behavior in vivo and enhanced photoacoustic/magnetic resonance imaging effects, enabling more accurate guidance for HIFU surgery. After surgery, the ADMOFs exploited the severely hypoxic tumor environment induced by HIFU, overcoming hypoxia‐associated drug resistance, and inducing immunogenic cell death. Finally, it effectively inhibited tumor growth and eliminated lung metastasis. Transcriptome studies revealed that this strategy significantly up‐regulated genes involved in apoptosis, cell cycle, and HIF‐1 signaling pathway while downregulating genes related to tumor proliferation and metastasis. These findings suggest that combining hypoxia‐activated chemo‐immunotherapy with HIFU is a promising strategy for enhancing cancer theranostics.

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Sorafenib blocks the activation of the HIF-2α/VEGFA/EphA2 pathway, and inhibits the rapid growth of residual liver cancer following high-intensity focused ultrasound therapy in vivo

Cited by 10 publications

References 30 publications

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies

Sorafenib Repurposing for Ophthalmic Delivery by Lipid Nanoparticles: A Preliminary Study

Metal‐Organic Framework‐Mediated Synergistic Hypoxia‐Activated Chemo‐Immunotherapy Induced by High Intensity Focused Ultrasound for Enhanced Cancer Theranostics

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