Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

Znati, Sami; Carter, Rob; Vásquez, Marcos; Westhorpe, Adam; Shahbakhti, Hassan; Prince, Jessica; Vlckova, Petra; Vellis, Chiara De; Bascal, Zainab; Loizidou, Marilena; Sharma, Ricky A.

doi:10.3390/cancers12071878

Cited by 13 publications

(12 citation statements)

References 55 publications

(77 reference statements)

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“…The antiagiogenic drug vandetanib is a TKI of vascular endothelial growth factor receptor-2 (VEGFR-2) and RET proto-oncogene with radio-enhancement potential. Znati et al [ 91 ] studied outcomes following combined treatment in pre-clinical models. In addition to conventional in vitro assays, the combination was studied in 3D spheroids and in a syngeneic mouse model of HCC.…”

Section: Radiosensitization Strategiesmentioning

confidence: 99%

Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination

Pérez-Romasanta

Portillo

Rodríguez-Gutierrez

et al. 2021

Cancers

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Stereotactic body radiotherapy (SBRT) is an emerging ablative modality for hepatocellular carcinoma (HCC). Most patients with HCC have advanced disease at the time of diagnosis, and therefore, are not candidates for definitive-intent therapies such as resection or transplantation. For this reason, various alternative local and regional therapies have been used to prevent disease progression, palliate symptoms, and delay liver failure. Stereotactic body radiation therapy is a non-invasive technique of delivering ablative doses of radiation to tumors while sparing normal or non-tumor hepatic tissue. Incorporation of SBRT in multidisciplinary HCC management is gradual, initially applied when other liver-directed therapies have failed or are contraindicated, and tried in combination with other locoregional or systemic therapies for more unfavorable conditions by more experienced teams. In order to improve SBRT therapeutic ratio, there has been much interest in augmenting the effect of radiation on tumors by combining it with chemotherapy, molecularly targeted therapeutics, nanoparticles, and immunotherapy. This review aims to synthesize available evidence to evaluate the clinical feasibility and efficacy of SBRT for HCC, and to explore novel radio-potentiation concepts by combining SBRT with novel therapeutics. It is expected that those approaches would result in improved therapeutic outcomes, even though many questions remain with regard to the optimal way to assemble treatments. Further trials are needed to evaluate and consolidate these promising therapies for HCC.

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Section: Radiosensitization Strategiesmentioning

confidence: 99%

Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination

Pérez-Romasanta

Portillo

Rodríguez-Gutierrez

et al. 2021

Cancers

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“…Also, the two arms had no difference in tumor stabilization rate ( 57 ). However, the combination of vandetanib with radiotherapy significantly enhanced radiation killing ( 58 ).…”

Section: Advances Of Other Multi-targeted Therapeutic Agents For Hccmentioning

confidence: 99%

Advances of Targeted Therapy for Hepatocellular Carcinoma

Niu

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma (HCC) is one of the common and fatal malignancies, which is a significant global health problem. The clinical applicability of traditional surgery and other locoregional therapies is limited, and these therapeutic strategies are far from satisfactory in improving the outcomes of advanced HCC. In the past decade, targeted therapy had made a ground-breaking progress in advanced HCC. Those targeted therapies exert antitumor effects through specific signals, including anti-angiogenesis or cell cycle progression. As a standard systemic therapy option, it tremendously improves the survival of this devastating disease. Moreover, the combination of targeted therapy with immune checkpoint inhibitor (ICI) has demonstrated more potent anticancer effects and becomes the hot topic in clinical studies. The combining medications bring about a paradigm shift in the treatment of advanced HCC. In this review, we presented all approved targeted agents for advanced HCC with an emphasis on their clinical efficacy, summarized the advances of multi-target drugs in research for HCC and potential therapeutic targets for drug development. We also discussed the exciting results of the combination between targeted therapy and ICI.

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“…Vandetanib, a FDA-approved medullary thyroid cancer therapy that inhibits EGFR ( 22 ), impairs the HIF-1 pathway by targeting the mTOR–HIF-1α–VEGF signaling axis in breast cancer cells ( 23 ) and increases survival in advanced medullary thyroid carcinoma ( 268 ). Vandetanib is able to radiosensitize and improve overall survival in xenografts ( 24 ). Phase I clinical trials proved Vandetanib’s safety in a (chemo)radiotherapy regimen for head and neck cancers ( 25 ) and brain metastasis of melanomas, although without differences for progression free survival (PFS) or overall survival (OS) ( 26 ).…”

Section: Improving Radiotherapy Response By Tumor Sensitizationmentioning

confidence: 99%

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

2021

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To meet the anabolic demands of the proliferative potential of tumor cells, malignant cells tend to rewire their metabolic pathways. Although different types of malignant cells share this phenomenon, there is a large intracellular variability how these metabolic patterns are altered. Fortunately, differences in metabolic patterns between normal tissue and malignant cells can be exploited to increase the therapeutic ratio. Modulation of cellular metabolism to improve treatment outcome is an emerging field proposing a variety of promising strategies in primary tumor and metastatic lesion treatment. These strategies, capable of either sensitizing or protecting tissues, target either tumor or normal tissue and are often focused on modulating of tissue oxygenation, hypoxia-inducible factor (HIF) stabilization, glucose metabolism, mitochondrial function and the redox balance. Several compounds or therapies are still in under (pre-)clinical development, while others are already used in clinical practice. Here, we describe different strategies from bench to bedside to optimize the therapeutic ratio through modulation of the cellular metabolism. This review gives an overview of the current state on development and the mechanism of action of modulators affecting cellular metabolism with the aim to improve the radiotherapy response on tumors or to protect the normal tissue and therefore contribute to an improved therapeutic ratio.

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Radiosensitisation of Hepatocellular Carcinoma Cells by Vandetanib

Cited by 13 publications

References 55 publications

Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination

Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination

Advances of Targeted Therapy for Hepatocellular Carcinoma

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

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