Management of Cutaneous and Extracutaneous Side Effects of Smoothened Inhibitor Therapy for Advanced Basal Cell Carcinoma

Mohan, Shalini; Chang, Anne Lynn S.

doi:10.1158/1078-0432.ccr-14-3180

Cited by 20 publications

(18 citation statements)

References 52 publications

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“…However, this is a difficult issue to analyse because (i) these patients are at risk of developing both BCC and SCC, and (ii) some BCCs can have squamous features, such as basosquamous carcinoma. 46 Further studies are needed to critically address this issue.…”

Section: Overviewmentioning

confidence: 99%

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting

Cass

Connor

Tabachnik³

2016

J Oncol Pharm Pract

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Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted.

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Section: Overviewmentioning

confidence: 99%

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting

Cass

Connor

Tabachnik³

2016

J Oncol Pharm Pract

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“…Innerhalb der ersten Therapiemonate kommt es häufig zu Haarausfall. Dieser kann auch nach Absetzen persistieren, bei einigen Patienten kam es zu keinem Haarwachstum mehr .…”

Section: Systemische Therapieunclassified

Aktuelle Diagnostik und Behandlung des Basalzellkarzinoms

Alter

Hillen

Leiter

et al. 2015

J Deutsche Derma Gesell

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Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor.

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“…To date, two inhibitors, vismodegib and sonidegib, have been approved by the US Food and Drug Administration (FDA) for treating locally advanced BCC. Despite the significant efficacy in treating BCC, these inhibitors suffer from the problem of acquired resistance, insufficient potency against solid tumors, and severe adverse effects . To overcome these drawbacks, new Hh inhibitor development strategies have been focused on designing Smo inhibitors with novel and diverse chemical structures or discovering inhibitors that selectively target upstream or downstream regulations of Smo.…”

Section: Introductionmentioning

confidence: 99%

“…To overcome these drawbacks, new Hh inhibitor development strategies have been focused on designing Smo inhibitors with novel and diverse chemical structures or discovering inhibitors that selectively target upstream or downstream regulations of Smo. Although many papers reviewed the fundamental functions and biological roles of the Hh pathway in cancer as well as their related modulators for cancer therapy, it remains a hot topic and much progress has been made in multiple directions . Therefore, this review summarizes different strategies and methodologies, and discusses the future therapeutic opportunities and challenges in this area.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the significant efficacy in treating BCC, these inhibitors suffer from the problem of acquired resistance, insufficient potency against solid tumors, and severe adverse effects. 9 To overcome these drawbacks, new Hh inhibitor development strategies have been focused on designing Smo inhibitors with novel and diverse chemical structures or discovering inhibitors that selectively target upstream or downstream regulations of Smo. Although many papers reviewed the fundamental functions and biological roles of the Hh pathway in cancer as well as their related modulators for cancer therapy, it remains a hot topic and much progress has been made in multiple directions.…”

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confidence: 99%

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Strategies to target the Hedgehog signaling pathway for cancer therapy

Xin

Cruz

et al. 2018

Medicinal Research Reviews

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Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma. The clinical success of vismodegib and sonidegib provided strong support for the development of Hh signaling pathway inhibitors via targeting the smoothened (Smo) receptor. Moreover, Hh signaling pathway inhibitors aimed to target proteins, which are downstream or upstream of Smo, have also been pursued based on the identification of additional therapeutic benefits. Recently, much progress has been made in Hh singling and inhibitors of this pathway. Herein, medicinal chemistry strategies, especially the structural optimization process of different classes of Hh inhibitors, are comprehensively summarized. Further therapeutic potentials and challenges are also discussed.

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Management of Cutaneous and Extracutaneous Side Effects of Smoothened Inhibitor Therapy for Advanced Basal Cell Carcinoma

Cited by 20 publications

References 52 publications

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting

Aktuelle Diagnostik und Behandlung des Basalzellkarzinoms

Strategies to target the Hedgehog signaling pathway for cancer therapy

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