Version 1
: Received: 3 June 2024 / Approved: 3 June 2024 / Online: 3 June 2024 (09:54:04 CEST)
How to cite:
Kilmister, E. J.; Tan, S. T. Malignant Melanoma: Insights into Cancer Stem Cells, Tumor Microenvironment, and the Renin-Angiotensin System. Preprints2024, 2024060054. https://doi.org/10.20944/preprints202406.0054.v1
Kilmister, E. J.; Tan, S. T. Malignant Melanoma: Insights into Cancer Stem Cells, Tumor Microenvironment, and the Renin-Angiotensin System. Preprints 2024, 2024060054. https://doi.org/10.20944/preprints202406.0054.v1
Kilmister, E. J.; Tan, S. T. Malignant Melanoma: Insights into Cancer Stem Cells, Tumor Microenvironment, and the Renin-Angiotensin System. Preprints2024, 2024060054. https://doi.org/10.20944/preprints202406.0054.v1
APA Style
Kilmister, E. J., & Tan, S. T. (2024). Malignant Melanoma: Insights into Cancer Stem Cells, Tumor Microenvironment, and the Renin-Angiotensin System. Preprints. https://doi.org/10.20944/preprints202406.0054.v1
Chicago/Turabian Style
Kilmister, E. J. and Swee T Tan. 2024 "Malignant Melanoma: Insights into Cancer Stem Cells, Tumor Microenvironment, and the Renin-Angiotensin System" Preprints. https://doi.org/10.20944/preprints202406.0054.v1
Abstract
Malignant melanoma (MM) is the most fatal form of skin cancer, accounting for 90% of all skin cancer deaths. Multiple dysregulated cellular pathways are involved in MM, including the MAPK/ERK and PI3K/PTEN/AKT pathways, which can be targeted with novel targeted inhibitors. However, these blockades can be overcome through the activation of alternative pathways, leading to treatment resistance. The high immunogenicity of MM has been exploited using checkpoint inhibitors resulting in improved survival outcomes of patients with advanced MM. However, their side effect profile and prohibitive cost remain a challenge and the survival outcomes for patients with metastatic MM remain poor. Treatment resistance has been attributed to the presence of cancer stem cells (CSCs), a small subpopulation of pluripotent, highly tumorigenic cells proposed to drive cancer progression, metastasis, and treatment resistance. CSCs reside within the MM tumor microenvironment (TME) regulated by the immune system, and the paracrine renin-angiotensin system (RAS), expressed in many cancer types, including MM. This article reviews the current treatment of advanced MM with targeted therapy and immune checkpoint blockers, highlights the emergence of mRNA vaccine. It also discusses the MM TME and its relationship with CSCs, and the local immune system and the paracrine RAS. It highlights the regulation of the MAPK/ERK and PI3K/AKT/mTOR pathways by the RAS via prorenin receptor and angiotensin II receptor 1, and how this relates to the CSCs and treatment resistance. This underscores the potential multi-modal therapeutic strategy by concurrent targeting of multiple components of the TME.
Keywords
melanoma; cancer vaccine; mRNA vaccine; renin-angiotensin system; drug repurposing; immunotherapy; embryonic stem cells; cancer stem cells
Subject
Medicine and Pharmacology, Dermatology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
