New Treatment Horizons in Uveal and Cutaneous Melanoma
Author:
Brănişteanu Daciana Elena12, Porumb-Andrese Elena12ORCID, Porumb Vlad34ORCID, Stărică Alexandra2, Moraru Andreea Dana5, Nicolescu Alin Codruț6ORCID, Zemba Mihail7, Brănişteanu Cătălina Ioana8, Brănişteanu George8, Brănişteanu Daniel Constantin25ORCID
Affiliation:
1. Department of Medical Specialties (III)-Dermatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 2. Railway Clinical Hospital, 700506 Iasi, Romania 3. Department of Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 4. Military Emergency Clinical Hospital “Dr. Iacob Czihac”, 700506 Iasi, Romania 5. Department of Ophthalmology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania 6. “Agrippa Ionescu” Emergency Clinical Hospital, 011773 Bucharest, Romania 7. Department of Ophthalmology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania 8. “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
Abstract
Melanoma is a complex and heterogeneous malignant tumor with distinct genetic characteristics and therapeutic challenges in both cutaneous melanoma (CM) and uveal melanoma (UM). This review explores the underlying molecular features and genetic alterations in these melanoma subtypes, highlighting the importance of employing specific model systems tailored to their unique profiles for the development of targeted therapies. Over the past decade, significant progress has been made in unraveling the molecular and genetic characteristics of CM and UM, leading to notable advancements in treatment options. Genetic mutations in the mitogen-activated protein kinase (MAPK) pathway drive CM, while UM is characterized by mutations in genes like GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. Chromosomal aberrations, including monosomy 3 in UM and monosomy 10 in CM, play significant roles in tumorigenesis. Immune cell infiltration differs between CM and UM, impacting prognosis. Therapeutic advancements targeting these genetic alterations, including oncolytic viruses and immunotherapies, have shown promise in preclinical and clinical studies. Oncolytic viruses selectively infect malignant cells, inducing oncolysis and activating antitumor immune responses. Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic virus for CM treatment, and other oncolytic viruses, such as coxsackieviruses and HF-10, are being investigated. Furthermore, combining oncolytic viruses with immunotherapies, such as CAR-T cell therapy, holds great potential. Understanding the intrinsic molecular features of melanoma and their role in shaping novel therapeutic approaches provides insights into targeted interventions and paves the way for more effective treatments for CM and UM.
Subject
Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics
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