Hedgehog signalling pathway inhibitors as cancer suppressing agents

Trieu N. Trinh, Eileen A. McLaughlin, Christopher P. Gordon, Adam McCluskey

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The Hedgehog (Hh) signalling pathway plays a pivotal role in the spatial and temporal regulation of cell proliferation and differentiation. By controlling the correct maturation of developing tissues and ensuring attainment of the correct size, position and the presence of fully functioning cellular structures, the Hh plays a pivotal role in development. Conversely aberrant Hh signalling is involved in Gorlin syndrome, basal cell carcinoma (the most common cancer in the world), and more than one third of all human medulloblastoma cases. In all of these cases, it is believed that deregulated Hh signalling leads to increased cell proliferation and tumour formation. Inhibition of the Hedgehog signalling pathway, is a recently validated anti-cancer drug target, with vismodegib (Erivedge™), approved by the U.S. Food and Drug Administration for the treatment of adult basal cell carcinoma. In this perspective we outline the current state of Hh pathway inhibitors with a particular focus on potential limitations of upstream Hh pathway inhibition in relation to resistance mutations and crosstalk pathways. Together, these limitations indicate that inhibition of downstream components, specifically the Gli family of transcription factors, may represent a next generation approach to suppress tumours associated with aberrant Hh pathway signalling.

Original languageEnglish
Pages (from-to)117-133
Number of pages17
JournalMedChemComm
Volume5
Issue number2
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

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HhAntag691
Basal Cell Carcinoma
Cell proliferation
Neoplasms
Cell Proliferation
Basal Cell Nevus Syndrome
Tumors
Medulloblastoma
Cells
Cellular Structures
United States Food and Drug Administration
Cell Differentiation
Crosstalk
Transcription Factors
Mutation
Tissue
Pharmaceutical Preparations

Cite this

Trinh, T. N., McLaughlin, E. A., Gordon, C. P., & McCluskey, A. (2014). Hedgehog signalling pathway inhibitors as cancer suppressing agents. MedChemComm, 5(2), 117-133. https://doi.org/10.1039/c3md00334e
Trinh, Trieu N. ; McLaughlin, Eileen A. ; Gordon, Christopher P. ; McCluskey, Adam. / Hedgehog signalling pathway inhibitors as cancer suppressing agents. In: MedChemComm. 2014 ; Vol. 5, No. 2. pp. 117-133.
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Trinh, TN, McLaughlin, EA, Gordon, CP & McCluskey, A 2014, 'Hedgehog signalling pathway inhibitors as cancer suppressing agents', MedChemComm, vol. 5, no. 2, pp. 117-133. https://doi.org/10.1039/c3md00334e

Hedgehog signalling pathway inhibitors as cancer suppressing agents. / Trinh, Trieu N.; McLaughlin, Eileen A.; Gordon, Christopher P.; McCluskey, Adam.

In: MedChemComm, Vol. 5, No. 2, 01.01.2014, p. 117-133.

Research output: Contribution to journalArticle

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Trinh TN, McLaughlin EA, Gordon CP, McCluskey A. Hedgehog signalling pathway inhibitors as cancer suppressing agents. MedChemComm. 2014 Jan 1;5(2):117-133. https://doi.org/10.1039/c3md00334e