Cytochrome P450 1A2 overcomes nuclear factor kappa B-mediated sorafenib resistance in hepatocellular carcinoma

Yu, Jianqing; Wang, Nuozhou; Gong, Zhongqin; Liu, Liping; Yang, Shengli; Chen, George G; Lai, Paul B.S.

doi:10.1038/s41388-020-01545-z

Cited by 26 publications

(20 citation statements)

References 46 publications

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“…Sorafenib is a first-line chemotherapy agent for advanced HCC patients (101). As an oral multikinase inhibitor, sorafenib plays an anti-cancer role by inhibiting cell proliferation and angiogenesis (102). Unfortunately, most HCC patients are prone to develop chemoresistance to sorafenib during treatment and ultimately gain poor clinical outcomes (102).…”

Section: Nf-kb-associated Chemoresistance In Hcc and Ncrnas-targeting Therapymentioning

confidence: 99%

“…As an oral multikinase inhibitor, sorafenib plays an anti-cancer role by inhibiting cell proliferation and angiogenesis (102). Unfortunately, most HCC patients are prone to develop chemoresistance to sorafenib during treatment and ultimately gain poor clinical outcomes (102). Given the central role of sorafenib in HCC therapy, it is urgent to further study the exact mechanisms of sorafenib resistance in HCC so as to improve chemosensitivity of HCC to sorafenib.…”

Section: Nf-kb-associated Chemoresistance In Hcc and Ncrnas-targeting Therapymentioning

confidence: 99%

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The Crosstalk Between Regulatory Non-Coding RNAs and Nuclear Factor Kappa B in Hepatocellular Carcinoma

Zhang

Shao

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma (HCC) is a highly lethal type of malignancies that possesses great loss of life safety to human beings worldwide. However, few effective means of curing HCC exist and its specific molecular basis is still far from being fully elucidated. Activation of nuclear factor kappa B (NF-κB), which is often observed in HCC, is considered to play a significant part in hepatocarcinogenesis and development. The emergence of regulatory non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is a defining advance in cancer biology, and related research in this branch has yielded many diagnostic and therapeutic opportunities. Recent studies have suggested that regulatory ncRNAs act as inhibitors or activators in the initiation and progression of HCC by targeting components of NF-κB signaling or regulating NF-κB activity. In this review, we attach importance to the role and function of regulatory ncRNAs in NF-κB signaling of HCC and NF-κB-associated chemoresistance in HCC, then propose future research directions and challenges of regulatory ncRNAs mediated-regulation of NF-κB pathway in HCC.

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Section: Nf-kb-associated Chemoresistance In Hcc and Ncrnas-targeting Therapymentioning

confidence: 99%

Section: Nf-kb-associated Chemoresistance In Hcc and Ncrnas-targeting Therapymentioning

confidence: 99%

The Crosstalk Between Regulatory Non-Coding RNAs and Nuclear Factor Kappa B in Hepatocellular Carcinoma

Zhang

Shao

et al. 2021

Front. Oncol.

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“…Strikingly, cytochrome P450 1A2 (CYP1A2) is downregulated in most HCCs and it negatively correlates with NF-κB p65 expression levels. Omeprazole is a CYP1A2 inducer, and its co-administration enhances sorafenib activity in preclinical HCC models by switching off nuclear NF-κB signaling [ 87 ]. Whether this combination could reduce sorafenib resistance in patients with HCC needs to be clarified.…”

Section: Csc Targeting and Therapeutic Implicationsmentioning

confidence: 99%

Hepatic Cancer Stem Cells: Molecular Mechanisms, Therapeutic Implications, and Circulating Biomarkers

Gramantieri

Giovannini

Suzzi

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC) is one of the deadliest cancers. HCC is associated with multiple risk factors and is characterized by a marked tumor heterogeneity that makes its molecular classification difficult to apply in the clinics. The lack of circulating biomarkers for the diagnosis, prognosis, and prediction of response to treatments further undermines the possibility of developing personalized therapies. Accumulating evidence affirms the involvement of cancer stem cells (CSCs) in tumor heterogeneity, recurrence, and drug resistance. Owing to the contribution of CSCs to treatment failure, there is an urgent need to develop novel therapeutic strategies targeting, not only the tumor bulk, but also the CSC subpopulation. Clarification of the molecular mechanisms influencing CSC properties, and the identification of their functional roles in tumor progression, may facilitate the discovery of novel CSC-based therapeutic targets to be used alone, or in combination with current anticancer agents, for the treatment of HCC. Here, we review the driving forces behind the regulation of liver CSCs and their therapeutic implications. Additionally, we provide data on their possible exploitation as prognostic and predictive biomarkers in patients with HCC.

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“…Therapeutic treatments are very complicated, as only a few patients, especially in the initial phase, can undergo surgery. Conversely, oral therapy with sorafenib, a kinase inhibitor, is indicated for patients in more advanced stages of cancer, but, unfortunately, is frequently associated with the onset of resistance within six months of treatment [ 12 , 13 , 14 , 15 , 16 , 17 ]. Furthermore, alongside this problem, long-term use of most chemotherapy drugs, including sorafenib, results in toxicity and ineffectiveness of the drug [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives

Chianese

Santella²,

Ambrosino

et al. 2021

Cancers

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According to the World Cancer Report, cancer rates have been increased by 50% with 15 million new cases in the year 2020. Hepatocellular carcinoma (HCC) is the only one of the most common tumors to cause a huge increase in mortality with a survival rate between 40% and 70% at 5 years, due to the high relapse and limitations associated with current therapies. Despite great progress in medicine, oncological research is always looking for new therapies: different technologies have been evaluated in clinical trials and others have been already used in clinics. Among them, oncolytic virotherapy represents a therapeutic option with a widespread possibility of approaches and applications. Oncolytic viruses are naturally occurring, or are engineered, viruses characterized by the unique features of preferentially infecting, replicating, and lysing malignant tumor cells, as well as activating the immune response. The combination of oncolytic virotherapy and chemical drugs are arousing great interest in the tumor treatment. In this scenario, novel and promising anticancer therapies comprise combinations of oncolytic viruses and epigenetic modulators or inhibitors of the signalling pathways. Combination treatments are required to improve the immune response and allow viral entry, replication, and diffusion between proximal cells. In this review, we summarize all combination therapies associated with virotherapy, including co-administered inhibitors of chromatin modifiers (combination strategies) and inserted target sites for miRNAs (recombination or arming strategies).

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Cytochrome P450 1A2 overcomes nuclear factor kappa B-mediated sorafenib resistance in hepatocellular carcinoma

Cited by 26 publications

References 46 publications

The Crosstalk Between Regulatory Non-Coding RNAs and Nuclear Factor Kappa B in Hepatocellular Carcinoma

The Crosstalk Between Regulatory Non-Coding RNAs and Nuclear Factor Kappa B in Hepatocellular Carcinoma

Hepatic Cancer Stem Cells: Molecular Mechanisms, Therapeutic Implications, and Circulating Biomarkers

Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives

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