Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2984 - 2984

Published: March 4, 2024

Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing mechanisms genesis. It highlights how mutations, particularly the BRAF, NRAS, c-KIT, GNAQ/GNA11 genes, affect critical signaling pathways. The evolution diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, biomarkers for early detection prognosis, also discussed. therapeutic landscape has transformed with targeted therapies immunotherapies, improving patient outcomes. paper examines efficacy, challenges, prospects treatments, including recent clinical trials emerging strategies. potential novel treatment strategies, neoantigen vaccines, adoptive cell transfer, microbiome interactions, nanoparticle-based combination therapy, explored. These emphasize challenges therapy resistance importance personalized medicine. underlines necessity evidence-based selection managing increasing global incidence melanoma.

Language: Английский

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Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 2, 2024

Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.

Language: Английский

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Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216758 - 216758

Published: Feb. 22, 2024

Language: Английский

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Relatlimab: a novel drug targeting immune checkpoint LAG-3 in melanoma therapy

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 10, 2024

Relatlimab is a type of human immunoglobulin G4 monoclonal blocking antibody. It the world's first Lymphocyte-Activation Gene-3 (LAG-3) inhibitor and third immune checkpoint with clinical application, following PD-1 CTLA-4. can bind to LAG-3 receptor which blocks interaction between its ligand reduce pathway-mediated immunosuppression promote T-cell proliferation, inducing tumor cell death. On 18 March 2022, U.S. FDA approved fixed-dose combination relatlimab developed by Bristol Myers Squibb nivolumab, under brand name Opdualag for treatment unresectable or metastatic melanoma in adult pediatric patients aged 12 older. This study comprehensively describes mechanism action trials brief overview drugs currently used melanoma.

Language: Английский

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Lymphocyte-activation gene 3 (LAG-3) as a promising immune checkpoint in cancer immunotherapy: From biology to the clinic

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 254, P. 155124 - 155124

Published: Jan. 11, 2024

Language: Английский

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Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 22, 2024

Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of gastric mucosa. The pathogenesis GC intricately linked to tumor microenvironment within which reside. Tumor-associated macrophages (TAMs) primarily differentiate peripheral blood monocytes and can be broadly categorized into M1 M2 subtypes. M2-type TAMs have been shown promote growth, tissue remodeling, angiogenesis. Furthermore, they actively suppress acquired immunity, leading poorer prognosis reduced tolerance chemotherapy. Exosomes, contain myriad biologically active molecules including lipids, proteins, mRNA, noncoding RNAs, emerged as key mediators communication between TAMs. exchange these via exosomes markedly influence consequently impact progression. Recent studies elucidated correlation various clinicopathological parameters GC, such size, differentiation, infiltration depth, lymph node metastasis, TNM staging, highlighting pivotal role in development metastasis. In this review, we aim comprehensively examine bidirectional TAMs, implications alterations on immune escape, invasion, metastasis targeted therapeutic approaches for efficacy potential drug resistance strategies.

Language: Английский

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Development of Personalized Strategies for Precisely Battling Malignant Melanoma

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 5023 - 5023

Published: May 4, 2024

Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond ability surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors targeted therapies. Acquired resistance to these therapies treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized specific and/or populations. Here, we review current landscape progress explore what oncology techniques may entail in scope melanoma. Our purpose provide an up-to-date summary tools at our disposal work circumvent common barriers faced when battling

Language: Английский

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Checkpoint Inhibitors in Dogs: Are We There Yet?

Cancers, Journal Year: 2024, Volume and Issue: 16(11), P. 2003 - 2003

Published: May 24, 2024

Immune checkpoint inhibitors (ICI) have revolutionised cancer treatment in people. checkpoints are important regulators of the body's reaction to immunological stimuli. The most studied immune molecules programmed death (PD-1) with its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) ligands CD80 (B7-1) CD86 (B7-2). Certain tumours can evade immunosurveillance by activating these targets. These proteins often upregulated cells tumour-infiltrating lymphocytes, allowing surveillance promote tumour growth. By blocking inhibitory checkpoints, ICI help restore system effectively fight cancer. Several studies investigated expression other human cancers shown their potential as therapeutic In recent years, there has been growing interest studying dogs cancer, a few small clinical trials already performed on species. Emerging veterinary oncology centred around developing validating canine-targeted antibodies. Among ICIs, anti-PD-1 anti-PD-L1 treatments stand out promising, mirroring success medicine over past decade. Nevertheless, efficacy caninized antibodies remains suboptimal, especially for canine oral melanoma. To enhance utilisation identification predictive biomarkers response thorough screening individual crucial. Such endeavours hold promise advancing personalised within practice, thereby improving outcomes. This article aims review current research literature about results dogs.

Language: Английский

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Immune Checkpoints and Cellular Landscape of the Tumor Microenvironment in Non-Melanoma Skin Cancer (NMSC)

Cells, Journal Year: 2024, Volume and Issue: 13(19), P. 1615 - 1615

Published: Sept. 26, 2024

Non-melanoma skin cancer (NMSC) is primarily categorized into basal cell carcinoma (BCC), the most prevalent form of cancer, and cutaneous squamous (cSCC), second common type. Both BCC cSCC represent a significant health burden, particularly in immunocompromised individuals elderly. The immune system plays pivotal role development progression NMSC, making it critical focus for therapeutic interventions. This review highlights key immunological targets cSCC, with on checkpoint molecules such as PD-1/PD-L1 CTLA-4, which regulate T activity contribute to evasion. also anti-tumor subsets within tumor microenvironment (TME), tumor-infiltrating lymphocytes (TILs) dendritic cells. Additionally, examines immunosuppressive elements TME, including regulatory cells (Tregs), myeloid-derived suppressor (MDSCs), tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), well their roles NMSC resistance therapy. Emerging strategies targeting these elements, monoclonal antibodies, are discussed potential enhance responses improve clinical outcomes. By elucidating landscape drawing comparisons melanoma, this transformative immunotherapy treating malignancies.

Language: Английский

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Advances in Immunotherapy and Targeted Therapy of Malignant Melanoma

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 225 - 225

Published: Jan. 17, 2025

Malignant melanoma (MM) is a malignant tumor, resulting from mutations in melanocytes of the skin and mucous membranes. Its mortality rate accounts for 90% all dermatologic tumor mortality. Traditional treatments such as surgery, chemotherapy, radiotherapy are unable to achieve expected results due MM's low sensitivity, high drug resistance, toxic side effects. As treatment advances, immunotherapy targeted therapy have made significant breakthroughs MM demonstrated promising application prospects. However, heterogeneity immune response causes more than half patients not benefit clinical therapy, which delays patient's condition them suffer adverse events' The combination can help improve therapeutic effects, delay mitigate This review provides comprehensive overview current development status research progress checkpoints, genes, their inhibitors, with view providing reference MM.

Language: Английский

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