Extracellular Vesicle‐Based Therapeutic Targeting of β‐Catenin to Modulate Anticancer Immune Responses in Hepatocellular Cancer

Matsuda, Akiko; Ishiguro, Kaori; Yan, Irene K.; Patel, Tushar

doi:10.1002/hep4.1311

Cited by 45 publications

(47 citation statements)

References 44 publications

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“…Likewise, a hyper-active Wnt/β-catenin cascade has been shown to play a crucial role in the progression, stemness, and drug resistance in OC [ 70 , 119 ]. Several miRNAs have been identified to modulate this cascade and thereby widely studied as screening markers or targets in different tumour settings [ 142 ].…”

Section: Discussionmentioning

confidence: 99%

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The Wnt Signalling Pathway: A Tailored Target in Cancer

Koni

Pinnarò

Brizzi

2020

IJMS

122

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Cancer is one of the greatest public health challenges. According to the World Health Organization (WHO), 9.6 million cancer deaths have been reported in 2018. The most common cancers include lung, breast, colorectal, prostate, skin (non-melanoma) and stomach cancer. The unbalance of physiological signalling pathways due to the acquisition of mutations in tumour cells is considered the most common cancer driver. The Wingless-related integration site (Wnt)/β-catenin pathway is crucial for tissue development and homeostasis in all animal species and its dysregulation is one of the most relevant events linked to cancer development and dissemination. The canonical and the non-canonical Wnt/β-catenin pathways are known to control both physiological and pathological processes, including cancer. Herein, the impact of the Wnt/β-catenin cascade in driving cancers from different origin has been examined. Finally, based on the impact of Extracellular Vesicles (EVs) on tumour growth, invasion and chemoresistance, and their role as tumour diagnostic and prognostic tools, an overview of the current knowledge linking EVs to the Wnt/β-catenin pathway is also discussed.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, since EVs are released within the TME, their contribution in cancer growth and progression has been extensively investigated [ 144 ]. EV shedding, blockade, or engineering have been proposed as innovative anti-tumour instruments for fine-tuning the Wnt/β catenin pathway [ 142 , 145 ].…”

Section: Discussionmentioning

confidence: 99%

The Wnt Signalling Pathway: A Tailored Target in Cancer

Koni

Pinnarò

Brizzi

2020

IJMS

122

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“…Combined application of inhibitors of the WNT/β‐catenin signaling pathway with immunocheckpoint blockers may be a more effective clinical treatment for sensitive cancers. The combination of PD‐1 antibody and biological nanoparticles of β‐catenin siRNA has been effective in animal experiments, providing an effective strategy for clinical cancer treatment 159,160 …”

Section: Abnormal Signaling Pathway Transduction and Related Protein mentioning

confidence: 99%

Study and analysis of antitumor resistance mechanism of PD1/PD‐L1 immune checkpoint blocker

Wang

2020

Cancer Medicine

115

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Immunocheckpoint proteins of tumor infiltrating lymphocytes play an important role in tumor prognosis in the course of tumor clinicopathology. PD‐1 (Programmed cell death protein 1) is an important immunosuppressive molecule. By binding to PD‐L1 (programmed cell death‐ligand 1), it blocks TCR and its costimulus signal transduction, inhibits the activation and proliferation of T cells, depletes the function of effector T cells, and enables tumor cells to achieve immune escape. In recent years, immunocheckpoint blocking therapy targeting the PD‐1/PD‐L1 axis has achieved good results in a variety of malignant tumors, pushing tumor immunotherapy to a new milestone, such as anti‐PD‐1 monoclonal antibody Nivolumab, Pembrolizumab, and anti‐PD‐L1 monoclonal antibody Atezolizumab, which are considered as potential antitumor drugs. It was found in clinical use that some patients obtained long‐term efficacy, but most of them developed drug resistance recurrence in the later stage. The high incidence of drug resistance (including primary and acquired drug resistance) still cannot be ignored, which limited its clinical application and became a new problem in this field. Due to tumor heterogeneity, current limited research shows that PD‐1 or PD‐L1 monoclonal antibody drug resistance may be related to the following factors: mutation of tumor antigen and antigen presentation process, multiple immune checkpoint interactions, immune microenvironment changes dynamically, activation of oncogenic pathways, gene mutation and epigenetic changes of key proteins in tumors, tumor competitive metabolism, and accumulation of metabolites, etc, mechanisms of resistance are complex. Therefore, it is the most urgent task to further elucidate the mechanism of immune checkpoint inhibitor resistance, discover multitumor universal biomarkers, and develop new target agents to improve the response rate of immunotherapy in patients. In this study, the mechanism of anti‐PD‐1/PD‐L1 drug resistance in tumors, the potential biomarkers for predicting PD‐1 acquired resistance, and the recent development of combination therapy were reviewed one by one. It is believed that, based on the complex mechanism of drug resistance, it is of no clinical significance to simply search for and regulate drug resistance targets, and it may even produce drug resistance again soon. It is speculated that according to the possible tumor characteristics, three types of treatment methods should be combined to change the tumor microenvironment ecology and eliminate various heterogeneous tumor subsets, so as to reduce tumor drug resistance and improve long‐term clinical efficacy.

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“…In addition to directly silencing the immunosuppressive genes, combination therapy with knock out/down oncogenic genes, through siRNA and immune checkpoint blockade therapy, may provide another promising method for cancer treatment. For example, Matsuda et al used the extracellular vesicles (EVs) to develop a biological nanoparticle-mediated delivery system for intrahepatic delivery of β-catenin siRNA to hepatocellular carcinoma (HCC)88. In this study, the β-catenin siRNA EVs and anti-PD-1-based therapy were systemically administrated together.…”

Section: Rna Nanotherapeutics For Tumor Immunotherapymentioning

confidence: 99%

RNA Nanotechnology-Mediated Cancer Immunotherapy

et al. 2020

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RNA molecules (e.g., siRNA, microRNA, and mRNA) have shown tremendous potential for immunomodulation and cancer immunotherapy. They can activate both innate and adaptive immune system responses by silencing or upregulating immune-relevant genes. In addition, mRNA-based vaccines have recently been actively pursued and tested in cancer patients, as a form of treatment. Meanwhile, various nanomaterials have been developed to enhance RNA delivery to the tumor and immune cells. In this review article, we summarize recent advances in the development of RNA-based therapeutics and their applications in cancer immunotherapy. We also highlight the variety of nanoparticle platforms that have been used for RNA delivery to elicit anti-tumor immune responses. Finally, we provide our perspectives of potential challenges and opportunities of RNA-based nanotherapeutics in clinical translation towards cancer immunotherapy.

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Extracellular Vesicle‐Based Therapeutic Targeting of β‐Catenin to Modulate Anticancer Immune Responses in Hepatocellular Cancer

Cited by 45 publications

References 44 publications

The Wnt Signalling Pathway: A Tailored Target in Cancer

The Wnt Signalling Pathway: A Tailored Target in Cancer

Study and analysis of antitumor resistance mechanism of PD1/PD‐L1 immune checkpoint blocker

RNA Nanotechnology-Mediated Cancer Immunotherapy

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