Signaling Pathways and Therapeutic Strategies in Advanced Basal Cell Carcinoma

Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increas...

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Vydáno v:	Cells (Basel, Switzerland) Ročník 12; číslo 21; s. 2534
Hlavní autoři:	Vallini, Giulia, Calabrese, Laura, Canino, Costanza, Trovato, Emanuele, Gentileschi, Stefano, Rubegni, Pietro, Tognetti, Linda
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland MDPI AG 27.10.2023
Témata:	Adult Antineoplastic Agents - adverse effects Basal cell carcinoma BET Cancer therapies Carcinoma, Basal Cell - drug therapy Carcinoma, Basal Cell - genetics Care and treatment Cellular signal transduction Drug resistance Epidemiology Genes Health aspects Hedgehog protein Hedgehog Proteins - metabolism Hedgehog-GLI pathway Humans immunotherapy Kinases Ligands Malignancy Melanoma Metastases Mutation Pathogenesis Proteins Radiation therapy Signal Transduction Skin cancer Skin Neoplasms - drug therapy Skin Neoplasms - genetics Sunburn & sun tanning Transcription activation Transcription factors Transplants & implants Tumors Italy United Kingdom > UK BET Hedgehog-GLI pathway basal cell carcinoma immunotherapy
ISSN:	2073-4409, 2073-4409
On-line přístup:	Získat plný text
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Popis
Shrnutí:	Non-melanoma skin cancers (NMSCs) are the most common human neoplasms world-wide. In detail, basal cell carcinoma (BCC) is the most frequent malignancy in the fair-skinned population. The incidence of BCC remains difficult to assess due to the poor registration practice; however, it has been increasing in the last few years. Approximately, 85% of sporadic BCCs carry mutations in Hedgehog pathway genes, especially in PTCH, SUFU and SMO genes, which lead to the aberrant activation of GLI transcriptional factors, typically silent in cells of adult individuals. The management of advanced BCC (aBCC), both metastatic (mBCC) and locally advanced BCC (laBCC), not candidates for surgical excision or radiotherapy, remains challenging. The discovery of mutations in the Hh signaling pathway has paved the way for the development of Hh pathway inhibiting agents, such as vismodegib and sonidegib, which have represented a breakthrough in the aBCC management. However, the use of these agents is limited by the frequent occurrence of adverse events or the development of drug resistance. In this review, we thoroughly describe the current knowledge regarding the available options for the pharmacological management of aBCCs and provide a forward-looking update on novel therapeutic strategies that could enrich the therapeutic armamentarium of BCC in the near future.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	2073-4409 2073-4409
DOI:	10.3390/cells12212534