Cancer stem cells and the SHH pathway in malignant melanoma: Therapeutic implications

Berrin Ozdil; Hüseyin Aktuğ

doi:10.19161/etd.1555155

TR EN

Malign melanomda kanser kök hücreleri ve SHH yolağı: Terapötik çıkarımlar

Öz

Malign melanom, melanositlerden kaynaklanan agresif bir cilt kanseridir. Melanom hem genetik hem de çevresel faktörlerden kaynaklanan karmaşık bir hastalıktır. Melanomda, kanser kök hücreleri (CSC'ler), kendini yenileme ve farklılaşma yetenekleri nedeniyle tümör ilerlemesinde, terapötik dirençte ve nüksde önemli bir rol oynar. Sonic Hedgehog (SHH) sinyal yolağı CSC'lerin önemli bir düzenleyicisidir ve hücre farklılaşması ve çoğalması için gereklidir. Embriyonik gelişimdeki ve kanserlerdeki rolü bilindiğinden, SHH yolağı malign melanomda CSC davranışını önemli ölçüde etkileyerek tümörijenisiteyi, metastazı ve tedavilere direnci teşvik eder. Bu yolak, Gli transkripsiyon faktörlerini içeren kanonik mekanizmaları ve hücre göçünü ve hücre iskeleti organizasyonunu etkileyen kanonik olmayan mekanizmaları koordine eder. SHH yolağının hedeflenmesi, Smoothened (Smo) ve Gli proteinleri gibi bileşenlere odaklanan inhibitörlerle umut verici bir terapötik strateji olarak ortaya çıkmıştır. Bununla birlikte, bu inhibitörlere karşı direnç, yeni terapötik kombinasyonların daha fazla araştırılmasını gerektirmektedir. Mevcut araştırmalar, daha etkili ve uzun süreli yanıtlar için SHH inhibitörlerini immünoterapilerle birleştirmeye odaklanmaktadır. SHH süreçlerini bozan hedefe yönelik ilaçlar, karsinogenezin temel nedenlerini ortadan kaldırmaya ve melanom hastalarının hayatta kalma oranlarını artırmaya çalışmaktadır.

Anahtar Kelimeler

Cancer stem cells and the SHH pathway in malignant melanoma: Therapeutic implications

Abstract

Melanoma is an aggressive skin cancer arising from melanocytes. Melanoma is a complex disease, sourced from genetic and environmental factors. Within melanoma, cancer stem cells (CSCs) play a crucial role in tumor progression, therapeutic resistance, and recurrence due to their capabilities for self-renewal and differentiation. The Sonic Hedgehog (SHH) signaling pathway is an important regulator of CSCs and is essential for cell differentiation and proliferation. Due to the known role in embryonic development and involvement in cancers, SHH pathway significantly affects CSC behavior in malignant melanoma, promoting tumorigenicity, metastasis, and resistance to therapies. This pathway coordinates canonical mechanisms involving Gli transcription factors and non-canonical mechanisms affecting cell migration and cytoskeletal organization. Targeting the SHH pathway has emerged as a promising therapeutic strategy, with inhibitors focusing on components like Smoothened (Smo) and Gli proteins. However, resistance to these inhibitors necessitates further exploration of novel therapeutic combinations. Current research focuses on combining SHH inhibitors with immunotherapies for more effective, long-lasting responses. Targeted medicines, which disrupt SHH processes, attempt to eliminate the fundamental causes of carcinogenesis and increase melanoma patient survival rates.

Keywords

Supporting Institution

Scientific Research Projects Coordination Unit at Ege University

Project Number

20785

Ethical Statement

It is a review study. There is no need for an ethics committee document.

Thanks

Scientific Research Projects Coordination Unit at Ege University

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Details

Primary Language

English

Subjects

Cancer Cell Biology

Journal Section

Review

Authors

Berrin Ozdil
0000-0001-6081-2308
Türkiye

Hüseyin Aktuğ ^*
0000-0003-4150-8495
Türkiye

Publication Date

June 10, 2025

Submission Date

September 24, 2024

Acceptance Date

January 27, 2025

Published in Issue

Year 2025 Volume: 64 Number: 2

DOI

https://doi.org/10.19161/etd.1555155

IZ

https://izlik.org/JA78FU59CX

Cite

RIS / Bibtex

Vancouver

1.Berrin Ozdil, Hüseyin Aktuğ. Cancer stem cells and the SHH pathway in malignant melanoma: Therapeutic implications. EJM. 2025 Jun. 1;64(2):415-23. doi:10.19161/etd.1555155