Anti-tumor Effect of Hedgehog Signaling Inhibitor, Vismodegib, on Castration-resistant Prostate Cancer

Ishii, Aya; Shigemura, Katsumi; Kitagawa, Koichi; Sung, Shian Ying; Chen, Kuan Chou; Chiang, Yi-Te; Liu, Ming Che; Fujisawa, Masato

doi:10.21873/anticanres.14514

Cited by 13 publications

(11 citation statements)

References 25 publications

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“…Besides, Hedgehog signaling‐mediated EMT, characterized by the overexpression of vimentin, Snail, N‐cadherin, and repression of E‐cadherin, ZO‐1, has been also reported in the metastasis of bladder cancer and breast cancer 345,346 . Inhibition of Hedgehog signaling with the administration of Vismodegib, the antagonist for PTCH1, is able to suppress EMT and cell proliferation of castration‐resistant prostate cancer 347 . Compelling evidence suggest that Hedgehog signaling promotes EMT via the key transcription factor Gli.…”

Section: Signalings In Embryonic Development Link To Emtmentioning

confidence: 99%

“…345,346 Inhibition of Hedgehog signaling with the administration of Vismodegib, the antagonist for PTCH1, is able to suppress EMT and cell proliferation of castration-resistant prostate cancer. 347 Compelling evidence suggest that Hedgehog signaling promotes EMT via the key transcription factor Gli. Indeed, the EMT-TF Snail is a transcriptional target of Gli1.…”

Section: Hedgehogmentioning

confidence: 99%

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Epithelial–mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities

Huang

Zhang

Zhou

et al. 2022

MedComm

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Epithelial–mesenchymal transition (EMT) is a program wherein epithelial cells lose their junctions and polarity while acquiring mesenchymal properties and invasive ability. Originally defined as an embryogenesis event, EMT has been recognized as a crucial process in tumor progression. During EMT, cell–cell junctions and cell–matrix attachments are disrupted, and the cytoskeleton is remodeled to enhance mobility of cells. This transition of phenotype is largely driven by a group of key transcription factors, typically Snail, Twist, and ZEB, through epigenetic repression of epithelial markers, transcriptional activation of matrix metalloproteinases, and reorganization of cytoskeleton. Mechanistically, EMT is orchestrated by multiple pathways, especially those involved in embryogenesis such as TGFβ, Wnt, Hedgehog, and Hippo, suggesting EMT as an intrinsic link between embryonic development and cancer progression. In addition, redox signaling has also emerged as critical EMT modulator. EMT confers cancer cells with increased metastatic potential and drug resistant capacity, which accounts for tumor recurrence in most clinic cases. Thus, targeting EMT can be a therapeutic option providing a chance of cure for cancer patients. Here, we introduce a brief history of EMT and summarize recent advances in understanding EMT mechanisms, as well as highlighting the therapeutic opportunities by targeting EMT in cancer treatment.

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Section: Signalings In Embryonic Development Link To Emtmentioning

confidence: 99%

Section: Hedgehogmentioning

confidence: 99%

Epithelial–mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities

Huang

Zhang

Zhou

et al. 2022

MedComm

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“…Hh signaling pathway is critically important for CSC functions, and therefore strategies to inhibit the pathway using pharmacological or genetic methods were studied. Cyclopamine, vismodegib, saridegib, and sonidegib are potent and specific SMO inhibitors, with clinical trials indicating therapeutic benefit for patients diagnosed with cancer [109][110][111][112][113]. Sonidegib was found to decrease CSC markers, including NANOG, OCT4, SOX2, and c-MYC [114].…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

Interaction between prostate cancer stem cells and bone microenvironment regulates prostate cancer bone metastasis and treatment resistance

Yao

Zhang

2022

J. Cancer

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Prostate cancer (PCa) is one of the most common cancers with increasing rates of incidence. Bone metastasis and drug resistance are the most serious threat faced by patients following a delayed diagnosis of cancer, which might lead to treatment failure and death. The theoretical model of cancer stem cells (CSCs) explains the diverse molecular characteristics of cancer as well as its relapse, metastasis and drug resistance. Prostate cancer involves heterogeneous cells community, including prostate cancer stem cells as an important component. These subtypes of cancer cells are usually monoclonal, expressing specific biomarkers and exhibiting self-renewal and differentiation capacity. Therefore, therapies that target CSCs might be more effective in overcome drug resistance and metastasis. Thus, anti-CSCs therapies differ from the traditional anti-proliferative approach. We focus here on reviewing the effects of prostate CSCs on bone metastasis and resistance to traditional treatment in PCa, and report new clinical strategies that address CSC-based tumorigenesis.

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“…Interestingly, in vitro studies utilizing PCa cells indicate that HH inhibition results in suppression of EMT. In a recent study, the newer Shh inhibitor vismodegib significantly inhibited EMT in CRPC cells and tumor growth in a mouse model [ 128 ].…”

Section: Molecular Events Governing Emt In Cancer Progressionmentioning

confidence: 99%

Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Papanikolaou

Vourda

Syggelos

et al. 2021

Cancers

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Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

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Anti-tumor Effect of Hedgehog Signaling Inhibitor, Vismodegib, on Castration-resistant Prostate Cancer

Cited by 13 publications

References 25 publications

Epithelial–mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities

Epithelial–mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities

Interaction between prostate cancer stem cells and bone microenvironment regulates prostate cancer bone metastasis and treatment resistance

Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

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