Advances in adoptive T-cell therapy for metastatic melanoma

Current Research in Translational Medicine, Journal Year: 2023, Volume and Issue: 71(3), P. 103404 - 103404

Published: July 1, 2023

Language: Английский

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The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3088 - 3088

Published: Nov. 9, 2021

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome limitations available therapeutic options, discovery development new, more effective, safer therapies required. In this review, different research steps involved in process antimelanoma drug evaluation selection are explored, including information regarding silico, vitro, vivo experiments, well clinical trial phases. Details given about cell lines assays perform both two- three-dimensional vitro screening candidates towards melanoma. For studies, murine models are, undoubtedly, widely for assessing potential new compounds study underlying mechanisms action. Here, main melanoma described other animal species. A section dedicated ongoing demonstrating wide interest successful efforts devoted therapy, particular at advanced stages disease, a final includes some considerations approval marketing by regulatory agencies. Overall, considerable commitment being directed continuous optimized experimental models, important understanding biology validation novel strategies.

Language: Английский

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Current Advances in PD-1/PD-L1 Blockade in Recurrent Epithelial Ovarian Cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 27, 2022

Immunotherapies have revolutionized the treatment of a variety cancers. Epithelial ovarian cancer is most lethal gynecologic malignancy, and rate advanced tumor progression or recurrence as high 80%. Current salvage strategies for patients with recurrent are rarely curative. Recurrent “cold tumor”, predominantly due to lack antigens an immunosuppressive microenvironment. In trials testing programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) blockade monotherapy, response was only 8.0-22.2%. this review, we illustrate status cold tumors in summarize existing clinical investigating PD-1/PD-L1 cancer. Increasing numbers immunotherapy combination been set up improve EOC. The current preclinical development therapy convert immune into hot their underlying mechanisms also reviewed. anti-PD-1/PD-L1 other immunomodulatory drugs therapies, such chemotherapy, antiangiogenic poly (ADP-ribose) polymerase inhibitors, adoptive cell therapy, oncolytic could be beneficial. Further efforts merited transfer these results broader application.

Language: Английский

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Overweight and Obesity Determine the Risk for Gastrointestinal Cancer in a Sex-Dependent Manner: A Retrospective Cohort Study of 287,357 Outpatients in Germany

Cancers, Journal Year: 2022, Volume and Issue: 14(4), P. 931 - 931

Published: Feb. 13, 2022

Cancer represents the second leading cause of death worldwide, implementing a major health care and socioeconomic burden. Overweight obesity, both which are dramatically on rise in highly less developed regions have been established as modifiable risk factors for development various tumor entities including gastrointestinal (GI) cancers such colorectal or gastric cancer. However, systematic data an association between excessive body fat GI cancer from Germany missing. Methods: A total 287,357 adult outpatients with available BMI value 2010 2019 were identified Disease Analyzer database (IQVIA). The main outcome was pre-obesity (BMI 25–30 kg/m2) obesity ≥ 30 compared to normal weight 18.5–25 incident diagnoses (including colon, rectum, stomach, pancreas, liver cancer). Results: Within observation period, proportion colon patients increased stepwise 0.5% 0.64% 0.71% 0.91% obese female male patients, respectively, confirmed multivariable regression models (ORfemale obesity: 1.23; 95% CI: 1.03–1.48; ORmale 1.43, 1.17–1.74). In contrast, revealed that significantly associated rectal (OR: 1.36, 1.01–1.84) well 1.79, 1.17–2.73) men only. Conclusions: Our suggest decisive factor rectal, cancer, partly sex-dependent manner. Since overweight factors, current results may help establish appropriate prevention lifestyle programs reduce incidence high morbidity mortality tumors future.

Language: Английский

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Understanding Necroptosis in Pancreatic Diseases

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 828 - 828

Published: June 13, 2022

Intermediate between apoptosis and necrosis, necroptosis is a regulated caspase-independent programmed cell death that induces an inflammatory response mediates cancer development. As our understanding improves, its role in the physiopathology of numerous diseases, including pancreatic has been reconsidered, especially pancreatitis cancer. However, exact pathogenesis remains elusive, even though some studies have conducted on these diseases. Its unique mechanisms action diseases are expected to bring prospects for treatment Therefore, it imperative further explore molecular mechanism order identify novel therapeutic options. This article introduces recent related research explores necroptosis-related pathways, provides theoretical foundation new targets

Language: Английский

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New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 26, 2023

Melanoma is a form of skin cancer that can rapidly invade distant organs. A distinctive feature melanomas their pigmentation status, as melanin present in most melanomas, whilst many metastatic tumors could become amelanotic. Besides the obvious malfunction key genes pathway, amelanotic bear characteristic molecular signature accounting for aggressivity. Using mass spectrometry-based proteomics we report here panel biomarkers aggressive melanoma differ from less invasive pigmented cells. The developed method allows label-free quantification proteins identified by LC-MS/MS analysis. We found set comprising AHNAK, MYOF, ANXA1, CAPN2, ASPH, EPHA2, THBS1, TGM2, ACTN4 along with involved cell adhesion/migration (integrins, PLEC, FSCN1, FN1) are highly expressed melanoma. Accompanying down regulation specific such tyrosinase and TYRP1, these type Interestingly, analysis hypoxia revealed abundance this normoxia was rather unaltered conditions. These therefore predict behaviour cells early stages tumor development thus serve prognostic. Applying algorithm to related databases including samples published independent laboratories/public confirm specificity newly signatures. Overall, begin unravel alterations how basic offers insights into assess clinical, pathological misdiagnosis differences between main subtypes

Language: Английский

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Melanoma—the therapeutic considerations in the clinical practice

Annals of Palliative Medicine, Journal Year: 2023, Volume and Issue: 12(6), P. 1355 - 1372

Published: July 11, 2023

Sola Adeleke, Somto Okoli, Anojan Augustine, Joao Galante, Aayushi Agnihotri, Mario Uccello, Aruni Ghose, Michele Moschetta, Stergios Boussios

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Hallmarks of the Tumour Microenvironment of Gliomas and Its Interaction with Emerging Immunotherapy Modalities

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13215 - 13215

Published: Aug. 25, 2023

Gliomas are aggressive, primary central nervous system tumours arising from glial cells. Glioblastomas the most malignant. They known for their poor prognosis or median overall survival. The current standard of care is overwhelmed by heterogeneous, immunosuppressive tumour microenvironment promoting immune evasion and proliferation. advent immunotherapy with its various modalities—immune checkpoint inhibitors, cancer vaccines, oncolytic viruses chimeric antigen receptor T cells NK cells—has shown promise. Clinical trials incorporating combination immunotherapies have overcome resistance yielded promising survival prognostic benefits. Rolling these new therapies out in real-world scenario a low-cost, high-throughput manner unmet need hour. These will practice-changing implications to glioma treatment landscape. Here, we review immunobiological hallmarks TME gliomas, how evades work that being conducted this interplay.

Language: Английский

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MicroRNA-155 and Disease-Related Immunohistochemical Parameters in Cutaneous Melanoma

Diagnostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1205 - 1205

Published: March 22, 2023

Cutaneous melanoma is a severe and life-threatening form of skin cancer with growing incidences. While novel interventions have improved prognoses for these patients, early diagnosis targeted treatment remains the most effective approach. MicroRNAs grown to good use as potential biomarkers detection targets treatment. miR-155 well-studied its role in tumor cell survival proliferation various tissues, although controversial. In silico data analysis was performed dbDEMC v.3 identify differentially expressed miRNA. We validated gene using TarBase v8.0 miRPath v3.0 determined protein-protein interactions target genes. One hundred forty patients (age range 21-90 years) cutaneous who underwent resection were included. Molecular assessment Real-Time RT-qPCR, clinicopathological associations, literature review different roles performed. Analysis reveals controversial findings. there evidence upregulation primary metastatic samples, others suggest decreased expression later-stage cases brain metastasis. has been overexpressed prior precancerous lesions, it found be dysregulated when compared benign nevi. associated favorable outcomes some studies, showed an association Patients high levels also noted reduction after receiving anti-PD-1 treatment, correlated more prolonged overall survival. our patient's cohort, 22.9% relapsed during 45% developed recurrence, factors such lymph node infiltration, mitotic index, positive staining CD117. Although revealed downregulation specimens non-cancer increased superficial spreading subtype (p = 0.005) any rate 0.010). The did not optimum cutoff values predict relapse, or mortality. conclusion, could have, part, prognostic utility melanoma. Further mechanistic studies are required unravel multifunctional

Language: Английский

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Comparative transcriptomic analysis reveals differences in gene expression and regulatory pathways between nonacral and acral melanoma in Asian individuals

The Journal of Dermatology, Journal Year: 2024, Volume and Issue: 51(5), P. 659 - 670

Published: March 12, 2024

Melanoma predominantly occurs in White individuals, which is associated with factors such as exposure to UV radiation and skin pigmentation. Despite its low incidence, melanoma the primary cause of cancer-related death Asia, typically areas sun exposure. In our previous whole-exome sequencing study, we identified mutational signature 12 most prevalent variant Asian patients, differing from common UV-associated 7 observed individuals. We also major differences between acral (AM) nonacral (NAM) terms signatures 7, 21, 22. Notably, few studies have investigated genomic AM NAM Therefore, this conducted transcriptomic examine disparities RNA expression NAM. Ribosomal depletion was performed enhance detection functionally relevant coding noncoding transcripts. Ingenuity pathway analysis revealed significant gene regulatory pathways The results indicate that genes involved cell cycle signaling or immune modulation programmed protein 1/programmed 1 ligand were differentially expressed AM. addition, high CDK4 variability AM, immunogenicity Overall, these findings provide further insights into pathogenesis serve a reference for future research on malignant disease.

Language: Английский

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