Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC)
Basal cell carcinoma (BCC) is one of the most common neoplasms in the population. A good prognosis and mainly non-aggressive development have made it underdiagnosed and excluded from the statistics. Due to the availability of efficient surgical therapy, BCC is sometimes overlooked in the search for...
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MDPI AG
2022-10-01
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| author | Paulina Chmiel Martyna Kłosińska Alicja Forma Zuzanna Pelc Katarzyna Gęca Magdalena Skórzewska |
| author_facet | Paulina Chmiel Martyna Kłosińska Alicja Forma Zuzanna Pelc Katarzyna Gęca Magdalena Skórzewska |
| author_sort | Paulina Chmiel |
| collection | DOAJ |
| description | Basal cell carcinoma (BCC) is one of the most common neoplasms in the population. A good prognosis and mainly non-aggressive development have made it underdiagnosed and excluded from the statistics. Due to the availability of efficient surgical therapy, BCC is sometimes overlooked in the search for novel therapies. Most clinicians are unaware of its complicated pathogenesis or the availability of effective targeted therapy based on Hedgehog inhibitors (HHI) used in advanced or metastatic cases. Nevertheless, the concomitance and esthetic burden of this neoplasm are severe. As with other cancers, its pathogenesis is multifactorial and complicated with a network of dependencies. Although the tumour microenvironment (TME), genetic aberrations, and risk factors seem crucial in all skin cancers, in BCC they all have become accessible as therapeutic or prevention targets. The results of this review indicate that a central role in the development of BCC is played by the Hedgehog (Hh) signalling pathway. Two signalling molecules have been identified as the main culprits, namely Patched homologue 1 (PTCH1) and, less often, Smoothened homologue (SMO). Considering effective immunotherapy for other neoplastic growths being introduced, implementing immunotherapy in advanced BCC is pivotal and beneficial. Up to now, the US Food and Drug Administration (FDA) has approved two inhibitors of SMO for the treatment of advanced BCC. Sonidegib and vismodegib are registered based on their efficacy in clinical trials. However, despite this success, limitations might occur during the therapy, as some patients show resistance to these molecules. This review aims to summarize novel options of targeted therapies in BCC and debate the mechanisms and clinical implications of tumor resistance. |
| first_indexed | 2024-03-09T20:29:10Z |
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| id | doaj.art-70f2b8eb321749c6821bb88fc4732625 |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:29:10Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-70f2b8eb321749c6821bb88fc47326252023-11-23T23:27:23ZengMDPI AGCells2073-44092022-10-011120321010.3390/cells11203210Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC)Paulina Chmiel0Martyna Kłosińska1Alicja Forma2Zuzanna Pelc3Katarzyna Gęca4Magdalena Skórzewska5Department of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, PolandDepartment of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, PolandDepartment of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, PolandDepartment of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, PolandDepartment of Surgical Oncology, Medical University of Lublin, 20-081 Lublin, PolandBasal cell carcinoma (BCC) is one of the most common neoplasms in the population. A good prognosis and mainly non-aggressive development have made it underdiagnosed and excluded from the statistics. Due to the availability of efficient surgical therapy, BCC is sometimes overlooked in the search for novel therapies. Most clinicians are unaware of its complicated pathogenesis or the availability of effective targeted therapy based on Hedgehog inhibitors (HHI) used in advanced or metastatic cases. Nevertheless, the concomitance and esthetic burden of this neoplasm are severe. As with other cancers, its pathogenesis is multifactorial and complicated with a network of dependencies. Although the tumour microenvironment (TME), genetic aberrations, and risk factors seem crucial in all skin cancers, in BCC they all have become accessible as therapeutic or prevention targets. The results of this review indicate that a central role in the development of BCC is played by the Hedgehog (Hh) signalling pathway. Two signalling molecules have been identified as the main culprits, namely Patched homologue 1 (PTCH1) and, less often, Smoothened homologue (SMO). Considering effective immunotherapy for other neoplastic growths being introduced, implementing immunotherapy in advanced BCC is pivotal and beneficial. Up to now, the US Food and Drug Administration (FDA) has approved two inhibitors of SMO for the treatment of advanced BCC. Sonidegib and vismodegib are registered based on their efficacy in clinical trials. However, despite this success, limitations might occur during the therapy, as some patients show resistance to these molecules. This review aims to summarize novel options of targeted therapies in BCC and debate the mechanisms and clinical implications of tumor resistance.https://www.mdpi.com/2073-4409/11/20/3210basal cell carcinomaBCChedgehog inhibitorsHHIpatched homologue 1PTCH1 |
| spellingShingle | Paulina Chmiel Martyna Kłosińska Alicja Forma Zuzanna Pelc Katarzyna Gęca Magdalena Skórzewska Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC) Cells basal cell carcinoma BCC hedgehog inhibitors HHI patched homologue 1 PTCH1 |
| title | Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC) |
| title_full | Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC) |
| title_fullStr | Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC) |
| title_full_unstemmed | Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC) |
| title_short | Novel Approaches in Non-Melanoma Skin Cancers—A Focus on Hedgehog Pathway in Basal Cell Carcinoma (BCC) |
| title_sort | novel approaches in non melanoma skin cancers a focus on hedgehog pathway in basal cell carcinoma bcc |
| topic | basal cell carcinoma BCC hedgehog inhibitors HHI patched homologue 1 PTCH1 |
| url | https://www.mdpi.com/2073-4409/11/20/3210 |
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