&lt;p&gt;Angiogenesis in Hepatocellular Carcinoma; Pathophysiology, Targeted Therapy, and Role of Imaging&lt;/p&gt;

Moawad, Ahmed W; Szklaruk, Janio; Lall, Chandana; Blair, Katherine J.; Kaseb, Ahmed O.; Kamath, Amita; Rohren, Scott A; Elsayes, Khaled M.

doi:10.2147/jhc.s224471

Cited by 60 publications

(39 citation statements)

References 95 publications

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“…Therefore preventing/blocking abrupt angiogenesis is an effective approach for HCC prevention. (Berretta et al, 2016; Morse et al, 2018; Moawad et al, 2020). Angiogenesis has a crucial role in promoting tumor growth (HCC) by releasing VEGF leading to the development of HCC (Pan et al., 2018).…”

Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

et al. 2021

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Chemopreventive approaches with food‐derived phytochemicals are progressively rising as a significant aspect of tumor management and control. Herein, we have showcased the major phytoconstituents belonging to the group of flavanoid, as anti‐cancer agents used for the treatment and prevention of hepatocellular carcinoma (HCC). Sorafenib is the sole drug used for the treatment of advanced HCC, but its clinical application is limited because of its severe adverse effects and drug resistance. Diet‐based chemoprevention seems to be the way forward for this disease of malignant nature. As HCC is derived from a chronic inflammatory milieu, the regular incorporation of bioactive phytochemicals in the diet will confer protection and prevent progression to hepatocarcinogenesis. Many preclinical studies proved that the health benefits of flavonoids confer cytotoxic potential against various types of cancers including hepatocellular carcinoma. As flavonoids with excellent safety profile are abundantly present in common vegetables and fruits, they can be better utilized for chemoprevention and chemosensitization in such chronic condition. This review highlights the plausible role of the eight most promising flavonoids (Curcumin, Kaempferol, Resveratrol, Quercetin, Silibinin, Baicalein, Galangin and Luteolin) as key orchestrators of chemoprevention in hepatocellular carcinoma with preclinical and clinical evidence. An attempt to address the challenges in its clinical translation is also included. This review also provides an insight into the close association of HCC and metabolic disorders which may further decipher the chemopreventive effect of dietary bioactive from a proof of concept to extensive clinical translation. Practical applications According to GLOBOCAN 2020 database, it is estimated that 905,677 new cases of liver cancer and approximately 830,180 deaths related to that. The cancer incidence and mortality are almost similar as it is diagnosed at an advanced stage in patients where systemic drug therapy is the sole approach. Due to the emergence of multidrug resistance and drug‐related toxicities, most of the patient can not adhere to the therapy regimen. Flavonoids are known to be a potential anticancer agent with an excellent safety profile. These are found to be effective preclinically against hepatocellular carcinoma through modulation of numerous pathways in hepatocarcinogenesis. But, the bioavailability issue, lack of well designed‐validated clinical evidence, the possibility of food–drug interaction etc limit its clinical utility. The research inputs mainly to overcome pharmacokinetic issues along with suitable validation of efficacy and toxicity will be a critical point for establishing flavonoids as an effective, safe, affordable therapeutics.

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Section: Molecular Mechanism Of the Anticancer Effect Of Flavonoidmentioning

confidence: 99%

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

et al. 2021

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“…Advanced hepatocellular carcinoma (HCC) has limited treatment options, where overall survival can be improved but no cure has been found [ 119 ]. Given the highly vascular nature of HCC, anti-angiogenic therapy is currently the recommended therapy for advanced stage disease [ 120 ].…”

Section: Anti-angiogenic Therapy In the Most Common Cancersmentioning

confidence: 99%

“…Given the highly vascular nature of HCC, anti-angiogenic therapy is currently the recommended therapy for advanced stage disease [ 120 ]. Sorafenib and lenvatinib are used as first-line treatments for advanced unresectable HCC [ 119 ]; however, both have numerous side effects [ 119 ]. Regorafenib and cabozantinib are tyrosine kinase inhibitors.…”

Section: Anti-angiogenic Therapy In the Most Common Cancersmentioning

confidence: 99%

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

Olejarz

Kubiak-Tomaszewska

Chrzanowska

et al. 2020

IJMS

181

101

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Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research.

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“…However, there are significant advances being made, especially with MRI, that allow imaging of angiogenesis-correlated parameters. This is beyond the scope of the current review, but interesting applications may be found in the following reviews [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status

Florea

Mottaghy

Bauwens

2021

IJMS

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Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status. After a structured PubMed search, the resulting publication list was screened for oncology related publications in animals and humans, disregarding any cardiovascular findings. The tracers identified can be subdivided into direct targeting of angiogenesis (i.e., vascular endothelial growth factor, laminin, and fibronectin) and indirect targeting (i.e., glucose metabolism, hypoxia, and matrix metallo-proteases, PSMA). Presenting pre-clinical and clinical data of most tracers proposed in the literature, the indirect targeting agents are not 1:1 correlated with angiogenesis factors but do have a strong prognostic power in a clinical setting, while direct targeting agents show most potential and specificity for assessing tumour vascularisation and vitality. Within the direct agents, the combination of multiple targeting tracers into one agent (multimers) seems most promising. This review demonstrates the present clinical applicability of indirect agents, but also the need for more extensive research in the field of direct targeting of angiogenesis in oncology. Although there is currently no direct tracer that can be singled out, the RGD tracer family seems to show the highest potential therefore we expect one of them to enter the clinical routine.

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<p>Angiogenesis in Hepatocellular Carcinoma; Pathophysiology, Targeted Therapy, and Role of Imaging</p>

Cited by 60 publications

References 95 publications

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

Cogent role of flavonoids as key orchestrators of chemoprevention of hepatocellular carcinoma: A review

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

Molecular Imaging of Angiogenesis in Oncology: Current Preclinical and Clinical Status

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