Hedgehog Inhibition as an Anti-Cancer Strategy

Raju, G. Praveen; Pham, Diane

doi:10.1016/b978-0-12-394622-5.00023-7

Cited by 10 publications

(8 citation statements)

References 57 publications

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“…Subsequent studies confirmed the expression of Hh pathway components in cancer tissue and cell lines, putative cancer stem cells and the stroma 26, 58-60 . The pattern of Hh ligand expression and its signaling components have been used to determine the direction of signaling with implications for developing anti-cancer strategies 61 . Typically canonical Hh signaling indicates that the ligand is produced in an epithelial cell and received by a stromal cell (Fig.…”

Section: Hedgehog In Gi Cancersmentioning

confidence: 99%

Inhibition of Hedgehog signaling in the gastrointestinal tract: Targeting the cancer microenvironment

Merchant

Saqui‐Salces

2014

Cancer Treatment Reviews

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This review summarizes emerging information regarding the Hedgehog (Hh) signaling pathway during neoplastic transformation in the gastrointestinal tract. Although there is a role for the well-established canonical pathway in which Hedgehog ligands interact with their receptor Patched, there is sufficient evidence that downstream components of the Hh pathway, e.g., Gli1, are hijacked by non-Hh signaling pathways to promote the conversion of the epithelium to dysplasia and carcinoma. We review the canonical pathway and involvement of primary cilia, and then focus on current evidence for Hh signaling in luminal bowel cancers as well as accessory organs, i.e., liver, pancreas and biliary ducts. We conclude that targeting the Hh pathway with small molecules, nutriceuticals and other mechanisms will likely require a combination of inhibitors that target Gli transcription factors in addition to canonical modulators such as Smoothened.

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Section: Hedgehog In Gi Cancersmentioning

confidence: 99%

Inhibition of Hedgehog signaling in the gastrointestinal tract: Targeting the cancer microenvironment

Merchant

Saqui‐Salces

2014

Cancer Treatment Reviews

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“…Accumulating evidence has shown that abnormal Hh signalling is implicated in a growing number of human malignancies . Malignancies related to this pathway can be derived either from ligand overexpression or mutations in components of the pathway .…”

Section: Discussionmentioning

confidence: 99%

Heparanase‐1 and components of the hedgehog signalling pathway are increased in untreated alveolar orbital rhabdomyosarcoma

Tang

Huang

et al. 2013

Clinical Exper Ophthalmology

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“…The Hedgehog (Hh) pathway was discovered and named due to the role of the pathway in Drosophila melanogaster development (Nusslein‐Volhard and Wieschaus, ). The pathway plays a variety of different roles in various cell types and is disrupted in several cancers (Raju and Pham, ). Studies have indicated that components of the Hh pathway are modulated in CML LSC in comparison to normal counterparts.…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

“…The Hh pathway is complex with signalling ligands, transmembrane receptors and various intracellular proteins (Raju and Pham, ). Simply, Hh ligands bind receptor Patched, which relieves repression on transmembrane protein smoothened (SMO), leading to a signal transduction cascade resulting in nuclear translocation of Gli transcription factors and various downstream effects.…”

Section: Hedgehog Pathwaymentioning

confidence: 99%

Targeting survival pathways in chronic myeloid leukaemia stem cells

Sinclair

Latif

Holyoake

2013

British J Pharmacology

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leukaemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a fusion oncogene BCR-ABL, which encodes a protein with constitutive TK activity. The implementation of tyrosine kinase inhibitors (TKIs) marked a major advance in CML therapy; however, there are problems with current treatment. For example, relapse occurs when these drugs are discontinued in the majority of patients who have achieved a complete molecular response on TKI and these agents are less effective in patients with mutations in the BCR-ABL kinase domain. Importantly, TKI can effectively target proliferating mature cells, but do not eradicate quiescent leukaemic stem cells (LSCs), therefore allowing disease persistence despite treatment. It is essential that alternative strategies are used to target the LSC population. BCR-ABL activation is responsible for the modulation of different signalling pathways, which allows the LSC fraction to evade cell death. Several pathways have been shown to be modulated by BCR-ABL, including PI3K/AKT/mTOR, JAK-STAT and autophagy signalling pathways. Targeting components of these survival pathways, alone or in combination with TKI, therefore represents an attractive potential therapeutic approach for targeting the LSC. However, many pathways are also active in normal stem cells. Therefore, potential targets must be validated to effectively eradicate CML stem cells while sparing normal counterparts. This review summarizes the main pathways modulated in CML stem cells, the recent developments and the use of novel drugs to target components in these pathways which may be used to target the LSC population. LINKED ARTICLES

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Hedgehog Inhibition as an Anti-Cancer Strategy

Cited by 10 publications

References 57 publications

Inhibition of Hedgehog signaling in the gastrointestinal tract: Targeting the cancer microenvironment

Inhibition of Hedgehog signaling in the gastrointestinal tract: Targeting the cancer microenvironment

Heparanase‐1 and components of the hedgehog signalling pathway are increased in untreated alveolar orbital rhabdomyosarcoma

Targeting survival pathways in chronic myeloid leukaemia stem cells

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