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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Pharmacologically inducing anoikis offers novel therapeutic opportunities in hepatocellular carcinoma
Yumin Wang1, Joshua S Fleishman2, Jinhua Wang3
1Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing 100049, China.
Abstract:
Tumor metastasis occurs in hepatocellular carcinoma (HCC), leading to tumor progression and therapeutic failure. Anoikis is a matrix detachment-induced apoptosis, also known as detachment-induced cell death, and mechanistically prevents tumor cells from escaping their native extracellular matrix to metastasize to new organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat HCC. Several natural and synthetic products induce anoikis in HCC cells and in vivo models. Here, we first briefly summarize the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in HCC metastasis. Then we discuss the therapeutic potential of pharmacological induction of anoikis as a potential treatment against HCC. Finally, we discuss the key limitations of this therapeutic paradigm and propose possible strategies to overcome them. Cumulatively this review suggests that the pharmacological induction of anoikis can be used a promising therapeutic modality against HCC.
Insights
Targeting anoikis (detachment-induced cell death) offers a promising strategy against hepatocellular carcinoma (HCC) metastasis. Inducing anoikis in cancer cells can prevent tumor progression and improve therapeutic outcomes in HCC treatment.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Tumor metastasis in hepatocellular carcinoma (HCC) drives disease progression and treatment resistance.
- Anoikis, or detachment-induced apoptosis, is a crucial cell death mechanism that normally prevents cancer cell dissemination.
- Understanding anoikis regulation is vital for developing effective HCC therapies.
Purpose of the Study:
- To review the molecular mechanisms and regulators of anoikis in HCC metastasis.
- To explore the therapeutic potential of pharmacologically inducing anoikis in HCC.
- To identify limitations and propose strategies for this therapeutic approach.
Main Methods:
- Literature review summarizing current knowledge on anoikis regulation in HCC.
- Analysis of natural and synthetic compounds that induce anoikis in HCC models.
- Discussion of therapeutic strategies and their challenges.
Main Results:
- Several agents have demonstrated the ability to induce anoikis in HCC cells and in vivo.
- Pharmacological induction of anoikis presents a viable therapeutic avenue for HCC.
- Key limitations and potential solutions for this treatment modality were identified.
Conclusions:
- The pharmacological induction of anoikis is a promising therapeutic strategy for hepatocellular carcinoma.
- Targeting anoikis can combat tumor progression and metastasis in HCC.
- Further research is needed to overcome current limitations and optimize this approach.
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