ArticleBMC cancer2018
A computational study of hedgehog signalling involved in basal cell carcinoma reveals the potential and limitation of combination therapy.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- EZH2 inhibitor and Vismodegib synergistically inhibit the growth and metastasis of medulloblastoma.Medical oncology (Northwood, London, England) · 2025Article
- The immunoreactivity of GLI1 and VEGFA is a potential prognostic factor in kidney renal clear cell carcinoma.BMC cancer · 2023Article
- Combating drug resistance in acute myeloid leukaemia by drug rotations: the effects of quizartinib and pexidartinib.Cancer cell international · 2021Article
- Hedgehog Pathway Inhibitors: Clinical Implications and Resistance in the Treatment of Basal Cell Carcinoma.Cureus · 2021Review
- Article
- Reverse engineering directed gene regulatory networks from transcriptomics and proteomics data of biomining bacterial communities with approximate Bayesian computation and steady-state signalling simulations.BMC bioinformatics · 2020Article
- Expression of the Sonic Hedgehog pathway components in clear cell renal cell carcinoma.Oncology letters · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations.
methodsWe investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC. To examine the potential for combination therapy or other treatments, we further performed knowledge-based simulations of SHH signalling, in the presence or absence of SMO and PI3K/Akt inhibitors.
resultsThe database analysis revealed that of 18 known mutations associated with Vismodegib-resistance, three were identified in the databases. Treatment of individuals carrying such mutations is thus liable to fail a priori. Analysis of the simulations suggested that a combined inhibition of SMO and the PI3K/Akt signalling pathway may provide an effective reduction in tumour proliferation. However, the inhibition dosage of SMO and PI3K/Akt depended on the activity of phosphodiesterases (PDEs). Under high PDEs activities, SMO became the most important control node of the network. By applying PDEs inhibition, the control potential of SMO decreased and PI3K appeared as a significant factor in controlling tumour proliferation.
conclusionsOur systems biology approach employs knowledge-based computer simulations to help interpret the large amount of data available in public databases, and provides application-oriented solutions for improved cancer resistance treatments.
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