Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck

Schulze, B.; Meißner, Markus; Ghanaati, Shahram; Burck, Iris; Rödel, Claus; Balermpas, Panagiotis

doi:10.1007/s00066-015-0902-7

Cited by 24 publications

(20 citation statements)

References 25 publications

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“…In phase II clinical trials, vismodegib treatment resulted in an increased median survival of one year in comparison with patients receiving a standard treatment [ 158 , 159 ]. These results suggested that vismodegib decreased the CSCs population through Hedgehog inhibition, being a promising strategy to the usage of vismodegib as a combinatory treatment with, for example, radiotherapy to target both non-CSC and CSC to remove all tumor cells [ 160 , 161 ].…”

Section: Treatments and Approachesmentioning

confidence: 99%

Drug Resistance Driven by Cancer Stem Cells and Their Niche

Prieto‐Vila¹,

Takahashi²,

Usuba³

et al. 2017

IJMS

420

335

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Drug resistance represents one of the greatest challenges in cancer treatment. Cancer stem cells (CSCs), a subset of cells within the tumor with the potential for self-renewal, differentiation and tumorigenicity, are thought to be the major cause of cancer therapy failure due to their considerable chemo- and radioresistance, resulting in tumor recurrence and eventually metastasis. CSCs are situated in a specialized microenvironment termed the niche, mainly composed of fibroblasts and endothelial, mesenchymal and immune cells, which also play pivotal roles in drug resistance. These neighboring cells promote the molecular signaling pathways required for CSC maintenance and survival and also trigger endogenous drug resistance in CSCs. In addition, tumor niche components such as the extracellular matrix also physically shelter CSCs from therapeutic agents. Interestingly, CSCs contribute directly to the niche in a bilateral feedback loop manner. Here, we review the recent advances in the study of CSCs, the niche and especially their collective contribution to resistance, since increasingly studies suggest that this interaction should be considered as a target for therapeutic strategies.

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Section: Treatments and Approachesmentioning

confidence: 99%

Drug Resistance Driven by Cancer Stem Cells and Their Niche

Prieto‐Vila¹,

Takahashi²,

Usuba³

et al. 2017

IJMS

420

335

View full text Add to dashboard Cite

show abstract

“…Hh inhibitors cyclopamine, LDE225 and GANT61 have been reported to sensitize cancer cells in vitro and in vivo to photon irradiation (115,165,(213)(214)(215). Several small clinical studies investigated the combination of photon irradiation with the Hh inhibitor vismodegib and reported that this combination has radiosensitizing effects in basal cell carcinomas (216)(217)(218). In addition, Hh signaling is an important pathway in CSC evolution and may have an impact on the intrinsic radioresistance of these cells.…”

Section: Inhibition Of Hedgehog Pathwaymentioning

confidence: 99%

Combination Therapy With Charged Particles and Molecular Targeting: A Promising Avenue to Overcome Radioresistance

et al. 2020

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Radiotherapy plays a central role in the treatment of cancer patients. Over the past decades, remarkable technological progress has been made in the field of conventional radiotherapy. In addition, the use of charged particles (e.g., protons and carbon ions) makes it possible to further improve dose deposition to the tumor, while sparing the surrounding healthy tissues. Despite these improvements, radioresistance and tumor recurrence are still observed. Although the mechanisms underlying resistance to conventional radiotherapy are well-studied, scientific evidence on the impact of charged particle therapy on cancer cell radioresistance is restricted. The purpose of this review is to discuss the potential role that charged particles could play to overcome radioresistance. This review will focus on hypoxia, cancer stem cells, and specific signaling pathways of EGFR, NFκB, and Hedgehog as well as DNA damage signaling involving PARP, as mechanisms of radioresistance for which pharmacological targets have been identified. Finally, new lines of future research will be proposed, with a focus on novel molecular inhibitors that could be used in combination with charged particle therapy as a novel treatment option for radioresistant tumors.

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“…If this radiosensitization also appears in cancer cells, the combination of Efavirenz with radiotherapy might improve tumor control. New combination strategies of radiosensitizing agents and radiotherapy may improve future treatment schemes ( 12 , 13 ). These results suggest that Efavirenz may be a promising new drug against cancer either alone or in combination with radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic effect of Efavirenz in BxPC‑3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation

et al. 2017

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The non-nucleoside reverse transcriptase inhibitor (NNRTI) Efavirenz is frequently used in human immunodeficiency virus treatment, but also efficient against cancer in mouse models. Its radiosensitizing effect makes it a promising drug for combination with radiotherapy. The efficacy of Efavirenz combined with irradiation was assessed with immunostaining of DNA-damage markers and colony formation assays in BxPC-3 pancreatic cancer cells. Gene expression and protein phosphorylation of the Efavirenz-sensitive BxPC-3 cells was compared to the resistant primary fibroblasts SBL-5. Oxidative stress, mitochondrial damage and cell death were studied with live-cell microscopy and flow cytometry. Combined Efavirenz and radiation significantly increased the number of γH2AX and phospho-ataxia telangiectasia mutated foci. Efavirenz and ionizing radiation had a synergistic effect using the clonogenic survival assay. Efavirenz selectively induced cell death in the BxPC-3 cells. The differing gene expression of cell cycle and apoptotic regulator genes in both cell cultures after Efavirenz treatment match with this selective effect against cancer cells. In the phosphoprotein array, an early phosphorylation of extracellular signal-related kinase 1/2 and p38 mitogen-activated protein kinase was notably detected in the cancer cells. The phosphorylation of AKT decreased in the cancer cells whereas it increased in the fibroblasts. Oxidative stress and mitochondrial membrane depolarization appeared in the cancer cells immediately after Efavirenz treatment, but not in the fibroblasts. Efavirenz has an anti-cancer effect against pancreatic cancer mainly by the induction of oxidative stress. The antitumor potential of Efavirenz and radiotherapy are additive.

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Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck

Abstract: The combination of vismodegib and radiation seems feasible and the initial results are promising. In our cohort, there was no increase in unexpected side effects. Further research is needed to evaluate the significance of this combined therapy.

Cited by 24 publications

References 25 publications

Drug Resistance Driven by Cancer Stem Cells and Their Niche

Drug Resistance Driven by Cancer Stem Cells and Their Niche

Combination Therapy With Charged Particles and Molecular Targeting: A Promising Avenue to Overcome Radioresistance

Cytotoxic effect of Efavirenz in BxPC‑3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation

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