Signal pathways of melanoma and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Dec. 20, 2021

Abstract Melanoma is the most lethal skin cancer that originates from malignant transformation of melanocytes. Although melanoma has long been regarded as a cancerous malignancy with few therapeutic options, increased biological understanding and unprecedented innovations in therapies targeting mutated driver genes immune checkpoints have substantially improved prognosis patients. However, low response rate inevitable occurrence resistance to currently available targeted posed obstacle path management obtain further amelioration. Therefore, it necessary understand mechanisms underlying pathogenesis more comprehensively, which might lead substantial progress approaches expand clinical options for therapy. In this review, we firstly make brief introduction epidemiology, subtypes, risk factors, current therapies. Then, signal pathways orchestrating pathogenesis, including genetic mutations, key transcriptional regulators, epigenetic dysregulations, metabolic reprogramming, crucial metastasis-related signals, tumor-promoting inflammatory pathways, pro-angiogenic systemically reviewed discussed. Subsequently, outline progresses checkpoints, well treatment resistance. Finally, prospects challenges development therapy, especially immunotherapy related ongoing trials, are summarized

Language: Английский

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Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 2, 2023

Abstract Despite centuries since the discovery and study of cancer, cancer is still a lethal intractable health issue worldwide. Cancer-associated fibroblasts (CAFs) have gained much attention as pivotal component tumor microenvironment. The versatility sophisticated mechanisms CAFs in facilitating progression been elucidated extensively, including promoting angiogenesis metastasis, inducing drug resistance, reshaping extracellular matrix, developing an immunosuppressive Owing to their robust tumor-promoting function, are considered promising target for oncotherapy. However, highly heterogeneous group cells. Some subpopulations exert inhibitory role growth, which implies that CAF-targeting approaches must be more precise individualized. This review comprehensively summarize origin, phenotypical, functional heterogeneity CAFs. More importantly, we underscore advances strategies clinical trials CAF various cancers, also progressions immunotherapy.

Language: Английский

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Fabricated Metal-Organic Frameworks (MOFs) as luminescent and electrochemical biosensors for cancer biomarkers detection

Biosensors and Bioelectronics, Journal Year: 2021, Volume and Issue: 197, P. 113738 - 113738

Published: Oct. 29, 2021

Language: Английский

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Melanoma Management: From Epidemiology to Treatment and Latest Advances

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4652 - 4652

Published: Sept. 24, 2022

Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response therapies currently available, which were restricted surgery, radiotherapy chemotherapy for many years. Advances knowledge about pathophysiological mechanisms of disease have allowed development new therapeutic classes, such as immune checkpoint small molecule kinase inhibitors. However, despite incontestable progress quality life survival rates patients, effectiveness still far from desired. Some adverse side effects resistance are main barriers. Thus, search better options resulted clinical trials that now investigating drugs and/or combinations. The low water solubility drugs, stability rapid metabolism limit potential use some compounds. research nanotechnology-based strategies being explored basis broad application different types nanosystems treatment melanoma. Future focus on challenges understanding make these more effective.

Language: Английский

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The Treatment of Advanced Melanoma: Therapeutic Update

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6388 - 6388

Published: June 7, 2022

Cutaneous melanoma is the main cause of death for skin cancer. The majority patients with a diagnosis have localized disease, which can be successfully treated surgical treatment. However, approach not curative advanced (AM). Indeed, management AM still challenging, since solid tumor highest number mutations and cancer cells capacity to evade immune system. In past, treatment relied on chemotherapeutic agents, without showing efficacy data. Recent knowledge pathogenesis as well introduction immunotherapies, targeted therapies vaccines, small molecules, combination has revolutionized management, promising results in terms effectiveness safety. aim this review assess discuss role emerging order obtain complete overview currently available options future perspectives.

Language: Английский

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Intracellular Self-Assembly of Peptides to Induce Apoptosis against Drug-Resistant Melanoma

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(16), P. 7337 - 7345

Published: March 31, 2022

Biosynthesis has been a diverse toolbox to develop bioactive molecules and materials, especially for fabricating modified peptides their assemblies induced by enzymes. Although desired chemical structures nanoarchitectures have achieved, the subsequent interferences of peptide with organelles cellular pathways still remain unsolved important challenges. Herein, we developed new tripeptide, phenylalanine-phenylalanine-tyrosine (Phe-Phe-Tyr, or FFY), which can be intracellularly oxidized in situ self-assemble into nanoparticles excellent interference capability microtubules ultimately reverse drug resistance melanoma. With catalysis tyrosinase, FFY was first melanin-like dimer (mFFY) diquinone structure further self-assembling mFFY assemblies, could inhibit self-polymerization tubulin induce severe G2/M arrest (13.9% higher than control). Afterward, mitochondrial dysfunction also overproduction cleaved caspase 3 (3.1 times control) PARP (6.3 higher), achieving high level resistant reversing without chemotherapeutic drugs. In vivo studies showed that melanoma tumor volumes were reduced 87.4% compared control groups after treatment peritumoral injections. Overall, this tyrosinase-induced tripeptide assembly demonstrated effective intrinsic apoptosis against drug-resistant melanoma, providing insight utilizing biomolecules interfere activate certain cancer.

Language: Английский

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Nano-drug delivery system targeting tumor microenvironment: A prospective strategy for melanoma treatment

Cancer Letters, Journal Year: 2023, Volume and Issue: 574, P. 216397 - 216397

Published: Sept. 18, 2023

Language: Английский

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Ultraviolet Radiation Biological and Medical Implications

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(3), P. 1924 - 1942

Published: Feb. 29, 2024

Ultraviolet (UV) radiation plays a crucial role in the development of melanoma and non-melanoma skin cancers. The types UV are differentiated by wavelength: UVA (315 to 400 nm), UVB (280 320 UVC (100 280 nm). can cause direct DNA damage forms cyclobutane pyrimidine dimers (CPDs) 6-4 photoproducts (6-4PPs). In addition, also indirectly through photosensitization reactions caused reactive oxygen species (ROS), which manifest as 8-hydroxy-2′-deoxyguanine (8-OHdG). Both indirect lead mutations genes that promote is largely influenced signaling melanocortin one receptor (MC1R), an essential synthesis melanin skin. UV-induced BRAF NRAS significant risk factors development. basal cell carcinoma (BCC) causing Hedgehog (Hh) pathway, dysregulates proliferation survival. induce squamous via TP53 gene upregulation MMPs stroma layer

Language: Английский

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Hypoxia-dependent drivers of melanoma progression

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: May 8, 2021

Abstract Hypoxia, a condition of low oxygen availability, is hallmark tumour microenvironment and promotes cancer progression resistance to therapy. Many studies reported the essential role hypoxia in regulating invasiveness, angiogenesis, vasculogenic mimicry response therapy melanoma. Melanoma an aggressive originating from melanocytes located skin (cutaneous melanoma), uveal tract eye (uveal melanoma) or mucosal membranes (mucosal melanoma). These three subtypes melanoma represent distinct neoplasms terms biology, epidemiology, aetiology, molecular profile clinical features. In this review, latest progress hypoxia-regulated pathways involved development all were discussed. We also summarized current knowledge on preclinical with drugs targeting Hypoxia-Inducible Factor-1, angiogenesis mimicry. Finally, we described available evidence investigating use Factor-1 inhibitors antiangiogenic drugs, alone combination other strategies, metastatic adjuvant settings cutaneous, Factor-independent have been regulate progression, but issue beyond scope review. As evident numerous discussed increasing promising results obtained novel therapies, could offer new perspectives practice order improve survival outcomes patients.

Language: Английский

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Systemic Therapy of Metastatic Melanoma: On the Road to Cure

Cancers, Journal Year: 2021, Volume and Issue: 13(6), P. 1430 - 1430

Published: March 20, 2021

This decade has brought significant survival improvement in patients with metastatic melanoma targeted therapies and immunotherapies. As our understanding of the mechanisms action these therapeutics evolves, even more impressive therapeutic success is being achieved through various combination strategies, including combinations different immunotherapies as well other modalities. review summarizes prospectively retrospectively generated clinical evidence on modern therapy, focusing immunotherapy therapy BRAF kinase inhibitors MEK (BRAF/MEK inhibitors), recent data presented at major conference meetings. The anti-PD-1 directed monoclonal antibody nivolumab CTLA-4 antagonist ipilimumab achieves unprecedented 5-year overall (OS) rates above 50%; however, toxicity high. For PD-1 monotherapy (nivolumab or pembrolizumab), toxicities are general manageable. Today, novel such immune checkpoint (ICIs) under investigation, for example cytokines oncolytic viruses (i.e., pegylated interleukin-2, talimogene laherparepvec). Furthermore, current studies investigate combined sequential use ICIs plus BRAF/MEK inhibitors. Several focus particularly poor prognosis patients, e.g., refractory melanoma, brain metastases, uveal melanoma. It hoped, road to cure, that new approaches further improve long term advanced

Language: Английский

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