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
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)
Article
Oncology
Li Li, Jing Zhao, Quanbao Zhang, Yifeng Tao, Conghuan Shen, Ruidong Li, Zhengyu Ma, Jianhua Li, Zhengxin Wang
Summary: This study demonstrated that HCC cells secrete Shh via exosomes to promote tumorigenesis through the activated Hedgehog pathway. The expression of Shh via exosomes is associated with later tumor stages and higher recurrence rates in liver cancer.
FRONTIERS IN ONCOLOGY
(2021)
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
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.
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
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)
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
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)
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
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)
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.
Article
Oncology
Sandra N. Freiberger, David Holzmann, Gregoire B. Morand, Martin Huellner, Mitchell P. Levesque, Reinhard Dummer, Viktor H. Koelzer, Niels J. Rupp
Summary: This study investigates novel biomarkers in mucosal melanoma that predict response to combined ipilimumab and nivolumab immunotherapy. The results suggest that the testis antigens CTAG1B (NY-ESO-1), MAGE-A3, and MAGE-A4 are predominantly expressed in responding tumors, and could potentially be used for future routine diagnostics to predict treatment outcomes.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Sarah A. Nadeau, Timothy G. Vaughan, Christiane Beckmann, Ivan Topolsky, Chaoran Chen, Emma Hodcroft, Tobias Schaer, Ina Nissen, Natascha Santacroce, Elodie Burcklen, Pedro Ferreira, Kim Philipp Jablonski, Susana Posada-Cespedes, Vincenzo Capece, Sophie Seidel, Noemi Santamaria de Souza, Julia M. Martinez-Gomez, Phil Cheng, Philipp P. Bosshard, Mitchell P. Levesque, Verena Kufner, Stefan SchmutzSchmutz, Maryam Zaheri, Michael Huber, Alexandra Trkola, Samuel Cordey, Florian Laubscher, Ana Rita Goncalves, Sebastien Aeby, Trestan Pillonel, Damien Jacot, Claire Bertelli, Gilbert Greub, Karoline Leuzinger, Madlen Stange, Alfredo Mari, Tim Roloff, Helena Seth-Smith, Hans H. Hirsch, Adrian Egli, Maurice Redondo, Olivier Kobel, Christoph Noppen, Louis du Plessis, Niko Beerenwinkel, Richard A. Neher, Christian Beisel, Tanja Stadler
Summary: Genome sequencing of SARS-CoV-2 in Switzerland revealed the number and persistence of virus introductions. Border closures in Switzerland significantly reduced case introductions, with up to a 98% reduction during the strictest measures. The partial lockdown in 2020 also shortened the time for introductions to die out. The study demonstrates the importance of genome sequencing data in understanding transmission dynamics.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Ossia M. Eichhoff, Corinne I. Stoffel, Jan Kasler, Luzia Briker, Patrick Turko, Gergely Karsai, Nina Zila, Verena Paulitschke, Phil F. Cheng, Alexander Leitner, Andrea Bileck, Nicola Zamboni, Anja Irmisch, Zsolt Balazs, Aizhan Tastanova, Susana Pascoal, Pal Johansen, Rebekka Wegmann, Julien Mena, Alaa Othman, Vasanthi S. Viswanathan, Judith Wenzina, Andrea Aloia, Annalisa Saltari, Andreas Dzung, Michael Krauthammer, Stuart L. Schreiber, Thorsten Hornemann, Martin Distel, Berend Snijder, Reinhard Dummer, Mitchell P. Levesque
Summary: The clinical management of NRAS-mutated melanomas is challenging due to resistance that arises through genetic, transcriptional, and metabolic adaptation. However, the adoption of a mesenchymal phenotype with a quiescent metabolic program in NRAS-mutated melanoma cells confers sensitivity to reactive oxygen species (ROS) induction, which can be inhibited by ROS inducers in combination with MAPK pathway inhibitors. The findings suggest that targeting both metabolic reprogramming and MAPK signaling could improve patient treatment in melanoma and other cancers.
Article
Oncology
Sara E. Cerminara, Phil Cheng, Lisa Kostner, Stephanie Huber, Michael Kunz, Julia-Tatjana Maul, Jette S. Bohm, Chiara F. Dettwiler, Anna Geser, Cecile Jakopovic, Livia M. Stoffel, Jelissa K. Peter, Mitchell Levesque, Alexander A. Navarini, Lara Valeska Maul
Summary: This study investigated the performance of 3D and 2D CNNs and dermatologists in early detection of melanoma. The 3D CNN outperformed the 2D CNN and achieved comparable sensitivity with dermatologists. Validating the classification of CNNs in real-life settings is emphasized.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Mateusz S. Wietecha, David Lauenstein, Michael Cangkrama, Sybille Seiler, Juyoung Jin, Andreas Goppelt, Manfred Claassen, Mitchell P. Levesque, Reinhard Dummer, Sabine Werner
Summary: Healing wounds and cancers share similarities at the cellular and molecular levels. The specific roles of healing phases are poorly understood. By comparing gene expression patterns, it was found that a wound signature during the resolution phase is associated with more severe skin cancer. Comparison of early and late-phase wound fibroblasts with cancer-associated fibroblasts (CAFs) identified distinct subtypes of CAFs. These findings provide insights into wound-regulated genes and matrix patterns with prognostic potential in skin cancer.
Article
Oncology
Marlene Langenbach, Sophie Giesler, Stefan Richtsfeld, Sara Costa-Pereira, Lukas Rindlisbacher, Tobias Wertheimer, Lukas M. Braun, Geoffroy Andrieux, Sandra Duquesne, Dietmar Pfeifer, Nadine M. Woessner, Hans D. Menssen, Sanaz Taromi, Justus Duyster, Melani Boerries, Tilman Brummer, Bruce R. Blazar, Susana Minguet, Patrick Turko, Mitchell P. Levesque, Burkhard Becher, Rober Zeiser
Summary: Treatment of metastatic melanoma with immune checkpoint inhibitors (ICI) has high response rates, but resistance to ICI impacts patient survival. In this study, the role of MDM2 inhibition in enhancing ICI therapy was investigated using mouse models and patient-derived melanoma cells. MDM2 inhibition induced expression of IL15 and MHC-II in melanoma cells through p53 induction. This enhanced antitumor immunity and induced anti-melanoma immune memory. In patients, increased IL15 and MHC-II expression correlated with better prognosis in WT melanoma but not TP53-mutated melanoma.
MOLECULAR CANCER RESEARCH
(2023)
Article
Oncology
E. L. Looman, P. F. Cheng, J. Lai-Kwon, L. Morgan, M. Wakkee, R. Dummer, F. Dimitriou
Summary: This study investigated the long-term symptom burden and impact on health-related quality of life of advanced melanoma patients treated with ICIs. The results showed that about 30% of patients reported long-term physical and emotional functioning issues, but overall health and quality of life were good.
Article
Oncology
Florian Maerkl, Mohamed-Reda Benmebarek, Julius Keyl, Bruno L. Cadilha, Martina Geiger, Clara Karches, Hannah Obeck, Melanie Schwerdtfeger, Stefanos Michaelides, Daria Briukhovetska, Sophia Stock, Jakob Jobst, Philipp Jie Mueller, Lina Majed, Matthias Seifert, Anna-Kristina Kluever, Theo Lorenzini, Ruth Gruenmeier, Moritz Thomas, Adrian Gottschlich, Richard Klaus, Carsten Marr, Michael von Bergwelt-Baildon, Simon Rothenfusser, Mitchell P. Levesque, Markus Vincent Heppt, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: Melanoma is an immune sensitive disease, and immune check point blockade has shown activity. However, TIL therapy after ICB failure has shown promising efficacy, indicating the potential of cellular therapies. To overcome limitations of TIL treatment, a controlled adoptive cell therapy approach using synthetic agonistic receptors and bispecific antibodies targeting melanoma-associated antigens is proposed.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Cell Biology
Athina Ganner, Antonia Philipp, Simon Lagies, Laura Wingendorf, Lu Wang, Felicitas Pilz, Thomas Welte, Kelli Grand, Soeren S. Lienkamp, Marinella Klein, Bernd Kammerer, Ian J. Frew, Gerd Walz, Elke Neumann-Haefelin
Summary: VHL inactivation is associated with the development of ccRCC, and VHL regulates SCD5 and fatty acid metabolism. SCD5 expression is regulated by VHL and HIF, and loss of SCD5 promotes cell proliferation and metabolic shift towards ceramide production.
Article
Oncology
Alina Miriam Mueller, Elisabeth Victoria Goessinger, Sara Elisa Cerminara, Lisa Kostner, Margarida Amaral, Stephanie Marie Huber, Lea Pauline Passweg, Laura Garcia Moreno, Daniel Bodenmann, Michael Kunz, Mitchell Paul Levesque, Julia-Tatjana Maul, Phil Fang Cheng, Alexander Andreas Navarini, Lara Valeska Maul
Summary: The incidence of melanoma has been increasing rapidly worldwide, and Switzerland has one of the highest rates in Europe. UV radiation is a major risk factor for skin cancer. This study investigated UV protective behavior and melanoma awareness in high-risk cohorts for melanoma. The results showed that melanoma patients used higher sun protection factors (SPF) compared to at-risk patients, and higher education levels were associated with more frequent use of high SPF. However, higher education levels also correlated with increased annual sun exposure. Participation in the study resulted in improved sun protection behavior.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marvin Thielert, Ericka C. M. Itang, Constantin Ammar, Florian A. Rosenberger, Isabell Bludau, Lisa Schweizer, Thierry M. Nordmann, Patricia Skowronek, Maria Wahle, Wen-Feng Zeng, Xie-Xuan Zhou, Andreas-David Brunner, Sabrina Richter, Mitchell P. Levesque, Fabian J. Theis, Martin Steger, Matthias Mann
Summary: Single-cell proteomics allows unbiased characterization of biological function and heterogeneity at the protein level. However, current limitations include proteomic depth, throughput, and robustness. In this study, we introduce a streamlined multiplexed workflow using mDIA to address these limitations. Our approach enables automated and complete dimethyl labeling of bulk or single-cell samples, without compromising proteomic depth. We also demonstrate the ability to quantify twice as many proteins per single cell compared to previous methods, and our workflow allows routine analysis of 80 single cells per day. Additionally, we combine mDIA with spatial proteomics to increase the throughput for microdissection and MS analysis, and successfully identify proteomic signatures of cells within distinct tumor microenvironments in primary cutaneous melanoma.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Markus Haake, Beatrice Haack, Tina Schaefer, Patrick N. Harter, Greta Mattavelli, Patrick Eiring, Neha Vashist, Florian Wedekink, Sabrina Genssler, Birgitt Fischer, Julia Dahlhoff, Fatemeh Mokhtari, Anastasia Kuzkina, Marij J. P. Welters, Tamara M. Benz, Lena Sorger, Vincent Thiemann, Giovanni Almanzar, Martina Selle, Klara Thein, Jacob Spaeth, Maria Cecilia Gonzalez, Carmen Reitinger, Andrea Ipsen-Escobedo, Kilian Wistuba-Hamprecht, Kristin Eichler, Katharina Filipski, Pia S. Zeiner, Rudi Beschorner, Renske Goedemans, Falk Hagen Gogolla, Hubert Hackl, Rogier W. Rooswinkel, Alexander Thiem, Paula Romer Roche, Hemant Joshi, Dirk Puehringer, Achim Woeckel, Joachim E. Diessner, Manfred Ruediger, Eugen Leo, Phil F. Cheng, Mitchell P. Levesque, Matthias Goebeler, Markus Sauer, Falk Nimmerjahn, Christine Schuberth-Wagner, Stefanie von Felten, Michel Mittelbronn, Matthias Mehling, Andreas Beilhack, Sjoerd H. van der Burg, Angela Riedel, Benjamin Weide, Reinhard Dummer, Joerg Wischhusen
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Fabienne Frohlich, Egle Ramelyte, Patrick Turko, Andreas Dzung, Sandra N. Freiberger, Joanna Mangana, Mitchell P. Levesque, Reinhard Dummer
Summary: Although immunotherapy and targeted therapy have improved melanoma survival, some patients rapidly progress and decease within months after a stage IV diagnosis. This study aimed to find genetic alterations that predict short or long survival in melanoma patients and found that a clock-like mutational signature was associated with poor survival, while a UV mutational signature was prognostic for longer survival. These findings suggest that mutational signatures could be valuable prognostic markers for melanoma.
Article
Chemistry, Medicinal
Lukas Kraehenbuehl, Stephanie Schneider, Laura Pawlik, Joanna Mangana, Phil Cheng, Reinhard Dummer, Barbara Meier-Schiesser
Summary: Recent progress in the treatment of advanced melanoma has led to improved survival, but also increased skin toxicity. This study investigated biopsy-proven cutaneous adverse events in melanoma treatment over 10 years. Skin adverse events were more common with targeted therapies compared to immune checkpoint blockade. A wide range of skin adverse events were observed, with different types associated with specific treatment classes.
Meeting Abstract
Oncology
Haley P. Wilson, Timothy J. Purwin, Claudia Capparelli, Phil F. Cheng, Mitch P. Levesque, Reinhard Dummer, Jessica Teh, Andrew E. Aplin