Treatment of basal cell carcinoma with vismodegib: future or present?

Velleman, Jos; Kaarela, Outi; Vranckx, Jan

doi:10.1080/00015458.2019.1658943

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…Another strategy to reduce the likelihood of developing acquired resistance is upfront shorter duration treatment prior to surgery, which may help reduce the time for acquired resistance to develop. HHIs are being studied as neoadjuvant therapy to reduce lesion size prior to surgery to optimize outcomes, as well as to enable the possibility of surgical excision in candidates previously unsuitable for surgery [56][57][58][59][60][61][62][63][64][65][66]. With this strategy, the development of HHI resistance may be less likely, as patients who respond to initial treatment will be able to have their tumors removed.…”

Section: Additional Strategies For Managing Hedgehog Inhibitor Resistancementioning

confidence: 99%

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma

Doan

Chen²,

Nawas

et al. 2021

Oncotarget

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Although basal cell carcinoma (BCC) is often managed successfully with surgery, patients with locally advanced BCC (laBCC) or metastatic BCC (mBCC) who are not candidates for surgery or radiotherapy have limited treatment options. Most BCCs result from aberrant Hedgehog pathway activation in keratinocyte tumor cells, caused by sporadic or inherited mutations. Mutations in the patched homologue 1 gene that remove its inhibitory regulation of Smoothened homologue (SMO) or mutations in SMO that make it constitutively active, lead to Hedgehog pathway dysregulation and downstream activation of GLI1/2 transcription factors, promoting cell differentiation and proliferation. Hedgehog inhibitors (HHIs) block overactive signaling of this pathway by inhibiting SMO and are currently the only approved treatments for advanced BCC. Two small-molecule SMO inhibitors, vismodegib and sonidegib, have shown efficacy and safety in clinical trials of advanced BCC patients. Although these agents are effective and tolerable for many patients, HHI resistance occurs in some patients. Mechanisms of resistance include mutations in SMO, noncanonical cell identity switching leading to tumor cell resistance, and non-canonical pathway crosstalk causing Hedgehog pathway activation. Approaches to managing HHI resistance include switching HHIs, HHI and radiotherapy combination therapy, photodynamic therapy, and targeting Hedgehog pathway downstream effectors. Increasing understanding of the control of downstream effectors has identified new therapy targets and potential agents for evaluation in BCC. Identification of biomarkers of resistance or response is needed to optimize HHI use in patients with advanced BCC. This review examines HHI resistance, its underlying mechanisms, and methods of management for patients with advanced BCC.

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Section: Additional Strategies For Managing Hedgehog Inhibitor Resistancementioning

confidence: 99%

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma

Doan

Chen²,

Nawas

et al. 2021

Oncotarget

View full text Add to dashboard Cite

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“… 4 Vismodegib is the first selective Hedgehog inhibitor approved for the treatment of laBCC or mBCC in adults who cannot be treated with surgery or radiotherapy. 5 …”

Section: Introductionmentioning

confidence: 99%

Vismodegib for treatment of periocular basal cell carcinoma – 6-year experience from a tertiary cancer center

Xavier¹,

Lopes²,

Bexiga³

et al. 2021

Anais Brasileiros de Dermatologia

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Background The treatment of advanced periocular basal cell carcinomas becomes a challenge as surgery may involve highly mutilating procedures. Vismodegib is the first selective hedgehog inhibitor approved for the treatment of locally advanced tumors or metastatic disease. Objective Analyze the results of treatment with vismodegib for advanced periocular basal cell carcinomas in a real-life setting of a reference center between 2014 and 2020. Methods Retrospective longitudinal study. The patient's demographic profile, comorbidities, tumor characteristics, and treatment outcomes were analyzed. Results A total of 13 patients were included. Median follow-up and treatment duration were 15.9 and 10.5 months, respectively. Objective clinical response rate was 76.9%: 30.8% had a complete response and 46.2% a partial response. The median duration of response was 13 months. Progressive disease was observed in 38.5% of cases, with a median of 19 months after the beginning of treatment. Eighty-four percent of the patients had at least one adverse event, and 61.54% needed to interrupt treatment temporarily or permanently to increase tolerability. Study limitations Being a retrospective study in a real-life setting, the evaluation of objective clinical response was subjective to physician appreciation. Conclusion Vismodegib is a safe and effective treatment for locally advanced basal cell carcinoma. To prevent recurrences, the drug should be used continually when tolerated. The role of neoadjuvant vismodegib before surgery is being investigated and might add an important step in searching for a definitive treatment for these cases.

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Vismodegib y sonidegib en el carcinoma de células basales localmente avanzado y metastásico: actualización acerca de los inhibidores de la vía de Hedgehog

Wijaya

Djawad

Wahab

et al. 2022

Actas Dermo-Sifiliográficas

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Treatment of basal cell carcinoma with vismodegib: future or present?

Cited by 4 publications

References 18 publications

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma

Vismodegib for treatment of periocular basal cell carcinoma – 6-year experience from a tertiary cancer center

Vismodegib y sonidegib en el carcinoma de células basales localmente avanzado y metastásico: actualización acerca de los inhibidores de la vía de Hedgehog

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