Review
Pharmacology & Pharmacy
Rupesh Jain, Sunil Kumar Dubey, Gautam Singhvi
Summary: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. While surgery is the main treatment, targeted combination therapies may be necessary in some cases. The Hedgehog signaling pathway is associated with BCC tumorigenesis and targeting it has potential therapeutic benefits. FDA-approved Hedgehog inhibitors show limited effectiveness against resistant tumors, highlighting the need for a better understanding of the pathway's mechanisms.
DRUG DISCOVERY TODAY
(2022)
Review
Medicine, General & Internal
Donatella Gambini, Emanuela Passoni, Gianluca Nazzaro, Giada Beltramini, Gianluca Tomasello, Michele Ghidini, Elisabetta Kuhn, Ornella Garrone
Summary: Basal cell carcinoma (BCC) is a common form of skin cancer that primarily affects elderly patients but can also occur in younger individuals, especially those who are immunocompromised or genetically predisposed. Recent studies have shown a link between BCC development, the Hedgehog (Hh) signaling pathway, and the immune system, specifically in response to Hh pathway inhibitors like vismodegib and sonidegib.
FRONTIERS IN MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Meghan W. Dukes, Thomas J. Meade
Summary: This article discusses the research progress and treatment methods for basal cell carcinoma (BCC). The focus of the study includes chemotherapeutics targeting the Hh pathway and genomic modulation for treatment and research models. Despite existing challenges, targeting the Hh pathway will continue to play a crucial role in research for designing more effective therapies.
Review
Cell Biology
Paulina Chmiel, Martyna Klosinska, Alicja Forma, Zuzanna Pelc, Katarzyna Geca, Magdalena Skorzewska
Summary: Basal cell carcinoma (BCC) is a common neoplasm with non-aggressive development and good prognosis. Targeted therapy based on Hedgehog inhibitors (HHI) has proven effective for advanced BCC. This review summarizes novel targeted therapies in BCC and discusses mechanisms and clinical implications of tumor resistance.
Article
Oncology
Elena Colombo, Cristina Gurizzan, Arianna Ottini, Francesca Caspani, Cristiana Bergamini, Laura D. D. Locati, Chiara Marchiselli, Andrea Alberti, Luigi Lorini, Lisa F. F. Licitra, Paolo Bossi, Carlo Resteghini
Summary: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are common human cancers with various risk factors. Current treatments include localized therapies and systemic therapies such as Sonic Hedgehog inhibitors and PD-1 checkpoint inhibitors. However, there is a lack of specific recommendations for advanced synchronous BCC/cSCC not amenable to local treatments. In this article, two elderly patients with synBCC/cSCC of the head and neck had successful combined therapy with cemiplimab and sonidegib, achieving significant clinical benefit without major adverse events. Further exploration of the synergistic effects of targeted therapies and immunotherapy is warranted.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Wenzhen Ge, Chieh- Chen, Ning Wu, Matthew G. Fury, Emily Ruiz, Jessica J. Jalbert
Summary: This study examined the real-world treatment patterns of Hedgehog pathway inhibitors for advanced basal cell carcinoma and found that discontinuation was common while reinitiation was uncommon.
Article
Dermatology
Egle Ramelyte, Mirjam C. Nageli, Robert Hunger, Rastine Merat, Olivier Gaide, Alexander A. Navarini, Antonio Cozzio, Nikolaus B. Wagner, Lara Valeska Maul, Reinhard Dummer
Summary: Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer in Switzerland and worldwide. This article provides Swiss recommendations for the diagnosis and management of BCC, based on extensive literature review and expert consensus. The recommendations consider the clinical subtype and recurrence rate of individual lesions, and offer evidence-based therapies for low-risk and high-risk tumors.
Review
Biochemistry & Molecular Biology
Toshihiko Hoashi, Naoko Kanda, Hidehisa Saeki
Summary: This review summarizes the clinical and pathological features of basal cell carcinoma, as well as the role of the hedgehog pathway and other crucial molecules in its carcinogenesis. Therapeutic strategies based on precise molecular mechanisms and biomarkers are discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Laura Eibenschutz, Silvia Caputo, Emanuela Camera, Anna Carbone, Vitaliano Silipo, Emilia Migliano, Caterina Aurizi, Carlo Cota, Pasquale Frascione, Barbara Bellei
Summary: Nevoid basal cell carcinoma syndrome (NBCCS) is a genetic disorder that predisposes individuals to basal cell carcinoma (BCC) due to mutations in genes related to the Hedgehog (Hh) pathway. Somatic mutations in this pathway are associated with sporadic BCC, and targeting this pathway with drugs like vismodegib and sonidegib could potentially be a therapeutic option. These drugs impact fibroblast functions supporting tumor growth and could be considered for BCC therapy regardless of the mutation status of Hh components in neoplastic cells.
Review
Oncology
Paolo Bossi, Paolo A. Ascierto, Nicole Basset -Seguin, Brigitte Dreno, Reinhard Dummer, Axel Hauschild, Peter Mohr, Roland Kaufmann, Giovanni Pellacani, Susana Puig, David Moreno-Ramirez, Caroline Robert, Alex Stratigos, Ralf Gutzmer, Paola Queirolo, Pietro Quaglino, Ketty Peris
Summary: This article presents the long-term management strategy for advanced BCC patients treated with systemic therapy. Hedgehog inhibitors Sonidegib and Vismodegib are first-line treatments for advanced BCC, but long-term use of hedgehog inhibitors is often challenging due to tolerability issues. However, various strategies for adverse effect management, such as dose interruptions, on-label alternate-day dosing, and supportive medications, are available.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Review
Dermatology
Arsh Patel, Jane S. Kim, Jason Liss, Lauren Howard, Sin-Ho Jung, Meenal Kheterpal
Summary: Management of patients with locally advanced basal cell carcinoma using traditional strategies has shown suboptimal outcomes. Targeted treatments, including hedgehog inhibitor therapy, have limitations as monotherapy. Evidence-based outcomes from literature support the use of adjunctive therapies post-HHIT to improve treatment response in laBCC patients.
DERMATOLOGIC THERAPY
(2021)
Review
Dermatology
Babette J. A. VERKOUTEREN, Kelly A. E. SINX, Marie G. H. C. REINDERS, Maureen J. B. AARTS, Klara MOSTERD
Summary: Some patients with basal cell carcinoma develop multiple tumors, with basal cell naevus syndrome being the most common underlying genetic disease. However, a significant portion of patients with multiple basal cell carcinomas have no known genetic cause. These patients, known as high-frequency basal cell carcinoma patients, experience a treatment burden similar to those with basal cell naevus syndrome. Hedgehog pathway inhibitors have been used as targeted therapy for basal cell carcinomas. This study reviews the literature on hedgehog pathway inhibitor therapy for patients with either basal cell naevus syndrome or high-frequency basal cell carcinoma, providing an overview of efficacy, safety, dosing regimens, tumor resistance and reoccurrence, and health-related quality of life.
ACTA DERMATO-VENEREOLOGICA
(2022)
Article
Biochemistry & Molecular Biology
Jun Wan, Hongji Dai, Xiaoli Zhang, Sheng Liu, Yuan Lin, Ally-Khan Somani, Jingwu Xie, Jiali Han
Summary: The majority of non-melanoma skin cancer cases are basal cell carcinoma and squamous cell carcinoma which originate from keratinocytes. The incidence of keratinocyte carcinomas in the US is over 5 million per year, three times higher than all other types of cancer combined. Research has shown significant variations in gene expression in these tumors, with novel findings including up-regulation of zinc finger encoding genes in human BCC and a novel link between hedgehog signaling, Wnt signaling, and the cilium.
Review
Biochemistry & Molecular Biology
Kristian Kaber Pedersen, Maria Helena Hoyer-Hansen, Thomas Litman, Merete Haedersdal, Uffe Hogh Olesen
Summary: Systemic treatment with hedgehog inhibitors (HHis) is available for basal cell carcinomas, but limited by adverse effects. Topical delivery methods may reduce adverse effects, but successful topical treatment depends on skin uptake, biological response, and time in tumor tissue. Current status of topical HHi delivery for BCCs is incomplete and there are barriers in terms of uptake, biodistribution, and biological response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Markus Heppt, Christoffer Gebhardt, Jessica C. Hassel, Mareike Alter, Ralf Gutzmer, Ulrike Leiter, Carola Berking
Summary: This article reviews treatment adjustments and novel therapeutic strategies for locally advanced basal cell carcinoma (laBCC). Hedgehog pathway inhibitors (HHIs) are the first-line therapy, but long-term treatment may cause toxicity and impact quality of life. Optimization of current treatment schedules and exploration of new combination strategies and drugs are urgently needed for laBCC.
