Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells

Youssef Al Hmada; Robert T Brodell; Naji Kharouf; Thomas W Flanagan; Abdulhadi A Alamodi; Sofie-Yasmin Hassan; Hosam Shalaby; Sarah-Lilly Hassan; Youssef Haikel; Mosaad Megahed; Simeon Santourlidis; Mohamed Hassan

doi:10.3390/cancers16020470

Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells

Cancers (Basel). 2024 Jan 22;16(2):470. doi: 10.3390/cancers16020470.

Authors

Youssef Al Hmada¹, Robert T Brodell¹, Naji Kharouf^{2

3}, Thomas W Flanagan⁴, Abdulhadi A Alamodi⁵, Sofie-Yasmin Hassan⁶, Hosam Shalaby⁷, Sarah-Lilly Hassan⁸, Youssef Haikel^{2

3

9}, Mosaad Megahed¹⁰, Simeon Santourlidis¹¹, Mohamed Hassan^{2

3

12}

Affiliations

¹ Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
² Institut National de la Santé et de la Recherche Médicale, University of Strasbourg, 67000 Strasbourg, France.
³ Department of Operative Dentistry and Endodontics, Dental Faculty, University of Strasbourg, 67000 Strasbourg, France.
⁴ Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, LA 70112, USA.
⁵ College of Health Sciences, Jackson State University, 310 W Woodrow Wilson Ave Ste 300, Jackson, MS 39213, USA.
⁶ Department of Pharmacy, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Dusseldorf, Germany.
⁷ Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
⁸ Department of Chemistry, Faculty of Science, Heinrich-Heine University Duesseldorf, 40225 Dusseldorf, Germany.
⁹ Pôle de Médecine et Chirurgie Bucco-Dentaire, Hôpital Civil, Hôpitaux Universitaire de Strasbourg, 67000 Strasbourg, France.
¹⁰ Clinic of Dermatology, University Hospital of Aachen, 52074 Aachen, Germany.
¹¹ Epigenetics Core Laboratory, Medical Faculty, Institute of Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University Düsseldorf, 40225 Dusseldorf, Germany.
¹² Research Laboratory of Surgery-Oncology, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.

Abstract

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% of melanomas demonstrating the BRAF mutation (BRAF^V600E). While the successful targeting of BRAF^V600E does improve overall survival, the long-term efficacy of available therapeutic options is limited due to adverse side effects and reduced clinical efficacy. Additionally, drug resistance develops rapidly via mechanisms involving fast feedback re-activation of MAPK signaling pathways. This article updates information relevant to the mechanisms of melanoma progression and resistance and particularly the mechanistic role of CSCs in melanoma progression, drug resistance, and recurrence.

Keywords: BRAF; CSCs; MAPK; PI3K; melanoma.

Publication types

Review

Grants and funding

This research received no external funding.