Sonidegib potentiates the cancer cells’ sensitivity to cytostatic agents by functional inhibition of ABCB1 and ABCG2 in vitro and ex vivo

Zhang, Yu; Vagiannis, Dimitrios; Budagaga, Youssif; Sabet, Ziba; Hanke, Ivo; Rozkoš, Tomáš; Hofman, Jakub

doi:10.1016/j.bcp.2022.115009

Cited by 12 publications

(13 citation statements)

References 33 publications

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“…Among these targets and drugs, sonidegib is a classic Hedgehog inhibitor [ 48 ]. Sonidegib is currently undergoing a phase I clinical trial (NCT04007744) for the treatment of NSCLC and is thought to be a viable candidate [ 49 ]. DSF partially inhibits GLI1 [ 50 ] in a copper‐dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Identification of tumour‐infiltrating myeloid subsets associated with overall survival in lung squamous cell carcinoma

Duan

Liu

et al. 2022

The Journal of Pathology

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Lung squamous cell carcinoma (LUSC) is a primary subtype of lung cancer with limited therapeutic options and poor prognosis, and tumour‐infiltrating myeloid cells (TIMs) are key regulators of LUSC. However, the correlation between the abundance of TIM subtypes and clinical outcomes of LUSC remains unexplored. This study aimed to develop and validate a prognostic model for low‐ and high‐risk patients with LUSC based on myeloid cell microenvironments. TIM markers in the tumoural (T) and stromal (S) regions were quantified using immunohistochemistry for 502 LUSC patients. L1‐penalized Cox regression was used to develop a myeloid survival score (MSS) model based on the training cohort, followed by validation in distinct cohorts from multiple centres. RNA sequencing and immunostaining were used to examine the mechanisms of myeloid cells in LUSC progression and predict potential drug targets and therapeutic agents. Of the 12 myeloid markers, CD163T, CD163S, and S100A12T were highly associated with overall survival (OS) in LUSC patients. The MSS of the three myeloid signatures accurately categorized LUSC patients into risk categories, with an observable difference in OS between the training and validation cohorts. Tumours with high MSS were associated with enhanced antioxidative ability and hedgehog signalling and a shift to a more pro‐tumorigenic microenvironment, accompanied by a reduced tumour cell immunogenicity and increased CD8+ T cell exhaustion patterns. Additionally, in high‐risk patients, potential drug targets and compounds regulating hedgehog signalling were identified. Our study provides the first prognostic myeloid signature for LUSC, which may help advance precision medicine. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Section: Discussionmentioning

confidence: 99%

Identification of tumour‐infiltrating myeloid subsets associated with overall survival in lung squamous cell carcinoma

Duan

Liu

et al. 2022

The Journal of Pathology

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“…Most of recent studies surrounding the drug-expelling ABC proteins, especially ABCB1 and ABCG2 which are major ABC transporters frequently overexpress in MDR cancer cells and can extrude a wide range of substance drugs, have been focused on their inhibitors which can attenuate their activity to extruding anti-tumor drugs 5 , 47 , 48 . It is accepted that the modulators of the ABC transporters have experienced three generations 49 .…”

Section: Drug Resistance-related Factors and Signalsmentioning

confidence: 99%

“…It is quite easy to achieve anti-tumor reagents such as inhibitors, however, as to how to improve the properties of these reagents as drugs, their biological availability, half-life, biocompatibility, and so on, are highly concerned as common issues that might make them more efficient and less harmful to the patients during clinical applications. Till now, hundreds of studies surrounding clinical application of the anti-tumor drugs for curation of MDR cancers, or those focusing on the anti-tumor drug systems with high potential for clinical translation have been published 1 , 5 , 11 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 .…”

Section: Prospects For Exploration Of Antitumor Drugs That Can Revers...mentioning

confidence: 99%

“…Based on target inhibition by small inhibitors, which are usually lack of specificity, many reports have shown that various factors may affect the drug-resistance in cancers, although modulation of the drug-resistance through these factors are sometimes not completely successful due to the highly frequent mutation within the genome of the cancer cells, which may largely elevate their drug-resistance during long-term drug treatment 4 . However, it will be meaningful to explore the factors promoting the development of drug-resistance, because at the least chemotherapies based on these findings have been demonstrated by clinical studies to have efficacy in improving the life-quality, as well as to potentially extend the life span of the patients 5 , 6 . Nevertheless, clarification of the factors related with early-stage MDR could timely benefit administration of the anti-tumor drugs and curation of the patient 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

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Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

Zhang

Ye²,

Chen³

et al. 2023

Acta Pharmaceutica Sinica B

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“…Vismodegib (GDC-0449) was the first FDA-approved inhibitor in 2012 that can bind to SMO to disrupt its consistent activation, primarily for the treatment of patients with recurrent, locally advanced or metastatic basal cell carcinoma (BBC) [415,416]. Several clinical trials have been conducted to test the anticancer effects of vismodegib as monotherapy or in combination with other agents in various conditions, including metastatic pancreatic cancer, prostate cancer, gastric cancer, recurrent glioblastoma, myelofibrosis, and acute myeloid leukemia [417][418][419][420][421]. Most of these trials are in stages I and II, as listed in Table 2.…”

Section: Targeting Smomentioning

confidence: 99%

The role of Hedgehog and Notch signaling pathway in cancer

Xia

Yang

et al. 2022

Mol Biomed

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Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.

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Sonidegib potentiates the cancer cells’ sensitivity to cytostatic agents by functional inhibition of ABCB1 and ABCG2 in vitro and ex vivo

Cited by 12 publications

References 33 publications

Identification of tumour‐infiltrating myeloid subsets associated with overall survival in lung squamous cell carcinoma

Identification of tumour‐infiltrating myeloid subsets associated with overall survival in lung squamous cell carcinoma

Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers

The role of Hedgehog and Notch signaling pathway in cancer

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