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Prof. Dr. Ketty Peris

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Institute of Dermatology, Catholic University of Rome, Fondazione Policlinico A. Gemelli, Largo Agostino Gemelli, 8-00168 Rome, Italy
Interests: dermato-oncology; melanoma; non-melanoma skin cancer; dermoscopy; immune-mediated diseases

Dr. Alessandro Di Stefani

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Guest Editor

Institute of Dermatology, Catholic University of Rome, Fondazione Policlinico A. Gemelli, Largo Agostino Gemelli, 8-00168 Rome, Italy
Interests: dermatopathology; dermato-oncology; dermoscopy; teledermatology

Special Issue Information

Dear Colleagues,

Basal cell carcinoma (BCC) is a slow-growing, locally-invasive malignant epidermal skin neoplasm that represents the most common malignancy in Caucasians, accounting for around 80% of all non-melanoma skin cancers, and its incidence is still on the rise worldwide. The clinical presentation of BCC can be extremely variable and the knowledge of defined high-risk clinico-pathological subtypes of BCC with different biologic behavior is required for appropriate clinical management of patients. The improvement of non-invasive diagnostic techniques, such as dermoscopy and the introduction of in vivo reflectance confocal microscopy, have allowed to increase the accuracy in the early identification of BCC aggressive variants, guiding clinician in decision-making regarding the need and suitability of various treatment strategies. The therapeutic armamentarium ranges from medical treatments and photodynamic therapy for low risk BCC, to surgical excision and radiation therapy for high risk BCC. In last years, molecular and genetic studies have shown that almost all BCC contain genetic alterations in the hedgehog signaling pathway, resulting in aberrant activation with uncontrolled proliferation and making it an optimal target for novel therapies. Thus, recently, novel therapeutic options are also available for the treatment of locally advanced and metastatic BCC that are not eligible for surgery or radiotherapy, consisting in small molecules that inhibit pathogenetic pathways. This Special Issue of IJMS gives insight in the evolving field of BCC regarding research, diagnosis, treatment modalities and clinical applications.

Dr. Ketty Peris
Dr. Alessandro Di Stefani
Guest Editors

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Keywords

skin neoplasm
non-melanoma skin cancer
basal cell carcinoma
BCC pathogenesis
diagnostic techniques
dermoscopy
reflectance confocal microscopy
target therapy

Published Papers (2 papers)

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Understanding the Molecular Genetics of Basal Cell Carcinoma

by Cristina Pellegrini, Maria Giovanna Maturo, Lucia Di Nardo, Valeria Ciciarelli, Carlota Gutiérrez García-Rodrigo and Maria Concetta Fargnoli

Int. J. Mol. Sci. 2017, 18(11), 2485; https://doi.org/10.3390/ijms18112485 - 22 Nov 2017

Cited by 152 | Viewed by 13001

Abstract

Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis. Full article

(This article belongs to the Special Issue Basal Cell Carcinoma)

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Open AccessCase Report

Appearance of New Cutaneous Superficial Basal Cell Carcinomas during Successful Nivolumab Treatment of Refractory Metastatic Disease: Implications for Immunotherapy in Early Versus Late Disease

by Philip R. Cohen, Shumei Kato, Aaron M. Goodman, Sadakatsu Ikeda and Razelle Kurzrock

Int. J. Mol. Sci. 2017, 18(8), 1663; https://doi.org/10.3390/ijms18081663 - 31 Jul 2017

Cited by 30 | Viewed by 8940

Abstract

Metastatic basal cell carcinoma may be treated with hedgehog pathway inhibitors, including vismodegib and sonidegib. However, patients can demonstrate resistance to these agents. We describe a man with metastatic basal cell carcinoma who did not respond well to vismodegib and sonidegib. Next generation sequencing of his metastatic liver tumor demonstrated a high tumor mutational burden (103 mutations per megabase) and the genomic amplification of PD-L1, both of which are features that predict response to anti-PD1/PD-L1 immunotherapy. Treatment with nivolumab, an anti-PD1 checkpoint inhibitor, resulted in near complete remission. Yet, he developed new primary cutaneous basal cell carcinomas while receiving immunotherapy and while his metastatic disease showed an ongoing response. His new superficial skin cancer had a lower tumor mutational burden (45 mutations per megabase) than the metastatic disease. Since immunotherapy response rates are higher in patients with more genomically complex tumors, our observations suggest that, in contrast with the premise of earlier treatment is better, which holds true for targeted and cytotoxic therapies, immunotherapy may be better suited to more advanced disease. Full article

(This article belongs to the Special Issue Basal Cell Carcinoma)

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