Cutaneous Melanoma: An Overview of Physiological and Therapeutic Aspects and Biotechnological Use of Serine Protease Inhibitors
Abstract
:1. Introduction
2. Epidemiology
3. Melanoma Subtypes
3.1. Lentigo Maligna
3.2. Desmoplastic Melanoma
3.3. Acral Melanoma
3.4. Spitz Melanoma
3.5. Mucosal Melanoma
3.6. Melanoma Arising in a Congenital Nevus
4. Melanoma Staging Phases
4.1. Primary Staging of Melanoma: Stages I and II
4.2. Melanoma Staging for Regional Lymph Nodes: Stage III
4.3. Metastatic Melanoma: Stage IV
5. Therapeutic Strategies and Medications Currently Used
5.1. Conventional Diagnosis and Therapy
5.1.1. Surgical Excision
5.1.2. Radiotherapy
5.1.3. Chemotherapy
5.2. Innovative Therapies
5.2.1. Topical Treatments
5.2.2. Targeted Anticancer Therapies: BRAF or MEK Mutation
5.2.3. Immunotherapy
5.2.4. Toll-like Receptor-9 (TLR-9) Agonists
5.2.5. Adoptive Cellular Therapy
5.2.6. Gene Therapy
6. Biotechnological Use of Serine Protease Inhibitors in the Anticancer Activity of Melanoma
7. Future Perspectives
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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TNM Classification 1 | Description |
---|---|
Primary staging of melanoma | |
Tis | Melanoma in situ—The melanoma is confined to the outermost layer of the skin (epidermis) and has not invaded the basal layer. Also called carcinoma in situ. |
T1 | The tumor is thin, usually less than 1 mm thick. May or may not have ulcerated. |
T2 | The tumor is of moderate thickness, 1 to 2 mm in depth. It may or may not have ulcerated. |
T3 | The tumor is thicker, 2 to 4 mm deep. It may or may not have ulcerated. |
T4 | The tumor is very thick, over 4 mm deep. It may or may not have ulcerated. |
Melanoma staging for regional lymph nodes | |
N0 | There is no evidence of regional lymph node metastasis. |
N1 | The melanoma has spread to a nearby lymph node but is micrometastasized (can only be detected with a microscope, cannot be seen or felt). |
N2 | The melanoma has spread to nearby lymph nodes and is considered macrometastatic metastasis (can be seen or felt). |
N3 | The melanoma has spread to nearby or distant lymph nodes, being multiple, grouped or with extranodal growth. |
Metastatic Melanoma | |
M0 | There is no evidence of distant metastasis. |
M1 | The melanoma has spread to other parts of the body beyond the primary tumor area and regional lymph nodes. |
Protease Inhibitor: Bowman-Birk Inhibitors (BBI) | |
---|---|
Source | Soybean (Glycine max) and other legumes. |
Type of protease inhibited | Serine proteases (trypsin and chymotrypsin). |
Biological effects | Inhibits cell proliferation and induce apoptosis in tumor cells. Demonstrates anticancer, anti-inflammatory, and antioxidant properties. Protects against oxidative damage and inflammation and may help prevent cancers such as melanoma. |
Research status | Studied in preclinical and early clinical models; showed efficacy in reducing tumor growth and cell protection. |
References | Lyu et al. [177]; Chen et al. [178]; Gitlin-Domagalska et al. [179]; Sato et al. [180]. |
Protease Inhibitor: Soybean Trypsin Inhibitor (Kunitz-Type) | |
Source | Soybean (Glycine max) and other legumes. |
Type of protease inhibited | Serine proteases (trypsin and chymotrypsin). |
Biological effects | Reduces tumoral cell proliferation and blocks cell invasion, especially in melanoma cells. Affects angiogenesis, decreasing the formation of blood vessels that feed tumors. |
Research status | In vitro and in vivo studies demonstrate efficacy in reducing melanoma cell growth. |
References | Shigetomi et al. [181]; Maria et al. [182]; Ranasinghe et al. [183]. |
Protease Inhibitor: Potato Trypsin Inhibitor | |
Source | Potato (Solanum tuberosum). |
Type of protease inhibited | Serine protease (trypsin). |
Biological effects | Affects cell cycle regulation, inhibiting cancer cell growth. Reduces tumoral metastasis and invasion in melanoma models by stabilizing the extracellular matrix. Demonstrates anti-inflammatory properties, which may be useful in autoimmune diseases. |
Research status | Promising results in laboratory studies and animal model. Focused on formulation for clinical use. |
References | Liu et al. [184] |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Boleti, A.P.D.A.; Jacobowski, A.C.; Monteiro-Alfredo, T.; Pereira, A.P.R.; Oliva, M.L.V.; Maria, D.A.; Macedo, M.L.R. Cutaneous Melanoma: An Overview of Physiological and Therapeutic Aspects and Biotechnological Use of Serine Protease Inhibitors. Molecules 2024, 29, 3891. https://doi.org/10.3390/molecules29163891
Boleti APDA, Jacobowski AC, Monteiro-Alfredo T, Pereira APR, Oliva MLV, Maria DA, Macedo MLR. Cutaneous Melanoma: An Overview of Physiological and Therapeutic Aspects and Biotechnological Use of Serine Protease Inhibitors. Molecules. 2024; 29(16):3891. https://doi.org/10.3390/molecules29163891
Chicago/Turabian StyleBoleti, Ana Paula De Araújo, Ana Cristina Jacobowski, Tamaeh Monteiro-Alfredo, Ana Paula Ramos Pereira, Maria Luiza Vilela Oliva, Durvanei Augusto Maria, and Maria Lígia Rodrigues Macedo. 2024. "Cutaneous Melanoma: An Overview of Physiological and Therapeutic Aspects and Biotechnological Use of Serine Protease Inhibitors" Molecules 29, no. 16: 3891. https://doi.org/10.3390/molecules29163891