Antibody drug conjugate: the “biological missile” for targeted cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: March 22, 2022

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to cytotoxic drug via chemical linker. It combines both the advantages highly specific targeting ability and potent killing effect achieve accurate efficient elimination cancer cells, which has become one hotspots for research development anticancer drugs. Since first ADC, Mylotarg

Language: Английский

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A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 18, 2023

Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, mainly associated with modest specificity therapeutic benefit, three key components form ADC (a monoclonal antibody bound to a cytotoxic drug via chemical linker moiety) achieve remarkable improvement terms targeted killing cancer cells and, while sparing healthy tissues, reduction systemic side effects caused by off-tumor toxicity. Based on their beneficial mechanism action, 15 ADCs have been approved date market approval Food Drug Administration (FDA), European Medicines Agency (EMA) and/or other international governmental agencies for use clinical oncology, hundreds undergoing evaluation preclinical phases. Here, our aim is provide comprehensive overview features revolving around strategy including structural targeting properties, role tumor microenvironment review providing discussion regarding toxicity profile, manifestations novel combination therapies. Finally, we briefly pathological contexts information manufacturing analytical characterization.

Language: Английский

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The Evolving Landscape of Antibody–Drug Conjugates: In Depth Analysis of Recent Research Progress

Bioconjugate Chemistry, Journal Year: 2023, Volume and Issue: 34(11), P. 1951 - 2000

Published: Oct. 11, 2023

Antibody–drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with selectivity monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows for higher doses drug be administered, potentially increasing efficacy. They currently among most promising classes in oncology, efforts expand their application nononcological indications combination therapies. Here we provide a detailed overview recent advances ADC research consider future directions challenges promoting this platform widespread therapeutic use. We examine data from CAS Content Collection, largest human-curated collection published scientific information, analyze publication landscape reveal exploration trends documents insights into area. also discuss evolution key concepts field, major technologies, development pipelines company focuses, disease targets, stages, investment trends. A comprehensive concept map has been created based on Collection. hope report can serve as useful resource understanding current state knowledge field ADCs remaining fulfill potential.

Language: Английский

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The Use of Immune Regulation in Treating Head and Neck Squamous Cell Carcinoma (HNSCC)

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 413 - 413

Published: Feb. 27, 2024

Immunotherapy has emerged as a promising new treatment modality for head and neck cancer, offering the potential targeted effective cancer management. Squamous cell carcinomas pose significant challenges due to their aggressive nature limited options. Conventional therapies such surgery, radiation, chemotherapy often have success rates can side effects. harnesses power of immune system recognize eliminate cells, thus represents novel approach with improve patient outcomes. In management squamous carcinoma (HNSCC), important contributions are made by immunotherapies, including adaptive therapy (ACT) checkpoint inhibitor therapy. this review, we focusing on latter. Immune inhibitors target proteins programmed death protein 1 (PD-1) cytotoxic T-lymphocyte-associated 4 (CTLA-4) enhance response against cells. The CTLA-4 inhibitors, ipilimumab tremelimumab, been approved early-stage clinical trials shown outcomes in terms tumor regression durable responses patients advanced HNSCC. Thus, holds promise overcoming limitations conventional therapies. However, further research is needed optimize regimens, identify predictive biomarkers, overcome resistance mechanisms. With ongoing advancements immunotherapy, future great transforming landscape oral providing hope patients.

Language: Английский

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The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Nov. 30, 2021

Background: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in progression of cancer. However, it is still unclear whether m6A/m5C/m1A-related long non-coding RNAs (lncRNAs) affect prognosis head neck squamous cell carcinoma (HNSCC). Methods: We summarized 52 genes, downloaded 44 normal samples 501 HNSCC tumor with RNA-seq data clinical information from The Cancer Genome Atlas (TCGA) database, then searched for genes co-expressed lncRNAs. adopt least absolute shrinkage selection operator (LASSO) Cox regression to obtain lncRNAs construct a prognostic signature HNSCC. Results: This based on six (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that high-risk subgroup has worse overall survival (OS) than low-risk subgroup. Moreover, results showed most immune checkpoint were significantly different between two risk groups (p < 0.05). Immunity microenvironment analysis contents NK resting, macrophages M2, neutrophils group lower those 0.05), while B cells navie, plasma cells, T regulatory (Tregs) contrary In addition, patients high mutational burden (TMB) had low burden. Conclusion: Our study elucidated how related prognosis, microenvironment, TMB future, these may become new choice immunotherapy

Language: Английский

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The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas

Cancers, Journal Year: 2022, Volume and Issue: 14(12), P. 2884 - 2884

Published: June 11, 2022

HNSCCs are the major progressive malignancy of upper digestive and respiratory organs. Malignant phenotypes regulated by pro- anti-tumoral activities immune modulatory cytokines associated with TMEs, i.e., a representative pro-inflammatory cytokine, interferon (IFN)-γ, plays role as an anti-tumor regulator against HNSCCs; however, IFN-γ also drives programmed death-ligand (PD-L) 1 expression to promote cancer stem cells. Interleukin (IL)-2 promotes cytotoxic activity T cells natural killer cells; endogenous IL-2 can regulatory (Tregs), resulting in protection HNSCCs. In this report, we first classified mentioned aspects cytokines, pro-/anti-inflammatory anti-inflammatory upon HNSCC phenotypes. TME HNSCCs, pro-tumoral modulation is mediated stromal cells, including CAFs, MDSCs, pDCs, TAMs. Therefore, evaluated functions chemokines that mediate crosstalk between tumor status lymph node metastasis important hallmark worse prognosis. We therefore possibility mediating metastases patients. mention therapeutic approaches using or immunotherapies target chemokines, signal molecules essential for evasion finally discuss HPV infection phenotypes, well prognostic significance serum cytokine levels

Language: Английский

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Current status and perspective of tumor immunotherapy for head and neck squamous cell carcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 26, 2022

Head and neck squamous cell carcinoma (HNSCC) have a high incidence mortality rate, investigating the pathogenesis potential therapeutic strategies of HNSCC is required for further progress. Immunotherapy considerable strategy due to its produce broad long-lasting antitumor response. However, immune escape, which involves mechanisms including dyregulation cytokines, perturbation checkpoints, recruitment inhibitory populations, limit efficacy immunotherapy. Currently, multiple immunotherapy been exploited, checkpoint inhibitors, costimulatory agonists, antigenic vaccines, oncolytic virus therapy, adoptive T transfer (ACT), epidermal growth factor receptor (EGFR)-targeted therapy. Each these has unique advantages, appropriate application immunotherapies in treatment significant value patients. Therefore, this review comprehensively summarizes escape characteristics different provide foundation consideration clinical HNSCC.

Language: Английский

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Bortezomib advanced mechanisms of action in multiple myeloma, solid and liquid tumors along with its novel therapeutic applications.

PubMed, Journal Year: 2023, Volume and Issue: 22, P. 146 - 168

Published: Jan. 1, 2023

Bortezomib (BTZ) is a first-in-class reversible and selective proteasome inhibitor. It inhibits the ubiquitin pathway that leads to degradation of many intracellular proteins. Initially, BTZ was FDA approved for treatment refractory or relapsed multiple myeloma (MM) in 2003. Later, its usage patients with previously untreated MM. In 2006, Mantle Cell Lymphoma (MCL) and, 2014, MCL. has been extensively studied either alone combination other drugs different liquid tumors especially However, limited data evaluated efficacy safety using solid tumors. this review, we will discuss advanced novel mechanisms action documented MM, Moreover, shed light on newly discovered pharmacological effects prevalent diseases.

Language: Английский

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Curcumin and analogues against head and neck cancer: From drug delivery to molecular mechanisms

Phytomedicine, Journal Year: 2023, Volume and Issue: 119, P. 154986 - 154986

Published: July 21, 2023

Language: Английский

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Exploring the frontiers: tumor immune microenvironment and immunotherapy in head and neck squamous cell carcinoma

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 31, 2024

Abstract The global prevalence of head and neck malignancies positions them as the sixth most common form cancer, with squamous cell carcinoma (HNSCC) representing predominant histological subtype. Despite advancements in multidisciplinary approaches molecular targeted therapies, therapeutic outcomes for HNSCC have only marginally improved, particularly cases recurrent or metastatic (R/MHNSCC). This situation underscores critical necessity development innovative strategies. Such strategies are essential not to enhance efficacy treatment but also minimize incidence associated complications, thus improving overall patient prognosis. Cancer immunotherapy represents a cutting-edge cancer that leverages immune system targeting destroying cells. It's applied multiple cancers, including melanoma lung offering precision, adaptability, potential long-lasting remission through memory. It is observed while patients responsive often experience prolonged benefits, limited subset demonstrates such responsiveness. Additionally, significant clinical challenges remain, resistance immunotherapy. biological characteristics, dynamic inhibitory changes, heterogeneity tumor microenvironment (TME) play roles its pathogenesis, evasion, resistance. review aims elucidate functions mechanisms anti-tumor cells extracellular components within TME. introduces several immunosuppressive agents commonly utilized immunotherapy, examines factors influencing effectiveness these treatments, provides comprehensive summary immunotherapeutic relevant HNSCC.

Language: Английский

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