Recent Advances and Challenges in Cancer Immunotherapy

Cancers, Journal Year: 2022, Volume and Issue: 14(16), P. 3972 - 3972

Published: Aug. 17, 2022

Cancer immunotherapy has revolutionized the field of oncology in recent years. Harnessing immune system to treat cancer led a large growth number novel immunotherapeutic strategies, including checkpoint inhibition, chimeric antigen receptor T-cell therapy and vaccination. In this review, we will discuss current landscape immuno-oncology research, with focus on elements that influence outcomes. We also highlight advances basic aspects tumor immunology, particular, role immunosuppressive cells within microenvironment regulating antitumor immunity. Lastly, how understanding immunology can lead development new strategies.

Language: Английский

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Senescence drives immunotherapy resistance by inducing an immunosuppressive tumor microenvironment

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 18, 2024

The potential of immune checkpoint inhibitors (ICI) may be limited in situations where cell fitness is impaired. Here, we show that the efficacy cancer immunotherapies compromised by accumulation senescent cells mice and context therapy-induced senescence (TIS). Resistance to immunotherapy associated with a decrease activation CD8 T within tumors. Elimination restores homeostasis tumor micro-environment (TME) increases survival response immunotherapy. Using single-cell transcriptomic analysis, observe injection ABT263 (Navitoclax) reverses exacerbated immunosuppressive profile myeloid TME. these also proliferation vitro abrogates resistance vivo. Overall, our study suggests use senolytic drugs before ICI constitute pharmacological approach improve effectiveness immunotherapies.

Language: Английский

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ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 14, 2024

At least 40% of human cancers are associated with aberrant ERK pathway activity (ERKp). Inhibitors targeting various effectors within the ERKp have been developed and explored for over two decades. Conversely, a substantial body evidence suggests that both normal cells and, notably to greater extent, cancer exhibit susceptibility hyperactivation ERKp. However, this vulnerability remains relatively unexplored. In review, we reexamine on selective lethality highly elevated in varying backgrounds. We synthesize insights proposed harnessing ERK-associated therapeutical approaches contextualize these established pharmacological cancer-targeting models. Moreover, compile intriguing preclinical findings agonism diverse Lastly, present conceptual framework target discovery regarding agonism, emphasizing utilization mutual exclusivity among oncogenes develop novel targeted therapies precision oncology.

Language: Английский

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Hallmarks of cancer resistance

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

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Leveraging the replication stress response to optimize cancer therapy

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 23(1), P. 6 - 24

Published: Nov. 2, 2022

Language: Английский

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Extracellular vesicle–based drug delivery in cancer immunotherapy

Drug Delivery and Translational Research, Journal Year: 2023, Volume and Issue: 13(11), P. 2790 - 2806

Published: June 1, 2023

Language: Английский

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Photothermal Effect of Gold Nanoparticles as a Nanomedicine for Diagnosis and Therapeutics

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(9), P. 2349 - 2349

Published: Sept. 19, 2023

Gold nanoparticles (AuNPs) have received great attention for various medical applications due to their unique physicochemical properties. AuNPs with tunable optical properties in the visible and near-infrared regions been utilized a variety of such as vitro diagnostics, vivo imaging, therapeutics. Among applications, this review will pay more recent developments diagnostic therapeutic based on photothermal (PT) effect AuNPs. In particular, PT has played an important role utilizing light, photoacoustic photon polymerase chain reaction (PCR), hyperthermia therapy. First, we discuss fundamentals detail understand background For ability efficiently convert absorbed light energy into heat generate enhanced acoustic waves can lead significant enhancements signal intensity. Integration PCR may open new opportunities technological innovation called photonic PCR, where is used enable fast accurate temperature cycling DNA amplification. Additionally, beyond existing thermotherapy AuNPs, be further applied cancer immunotherapy. Controlled damage cells triggers immune response, which useful obtaining better outcomes combination checkpoint inhibitors or vaccines. Therefore, examines nanomedicine among understands basic principles, advantages disadvantages each technology, importance multidisciplinary approach. Based this, it expected that help current status development direction nanoparticle-based disease diagnosis methods treatment methods, hope inspire innovative technologies.

Language: Английский

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Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: June 22, 2023

The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape have been identified. These include not only processes associated with tumor, or stromal cells, but also humoral, metabolic, genetic and epigenetic factors TME. identification has enabled development small molecules, nanomedicines, checkpoint inhibitors, adoptive cell that can reprogram TME shift host response towards promoting an antitumor effect. approaches translated into series breakthroughs in therapies, some which already implemented clinical practice. In present article authors provide overview most important immunosuppression implications for targeted against different cancers.

Language: Английский

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Biomarkers and computational models for predicting efficacy to tumor ICI immunotherapy

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

Published: March 8, 2024

Numerous studies have shown that immune checkpoint inhibitor (ICI) immunotherapy has great potential as a cancer treatment, leading to significant clinical improvements in numerous cases. However, it benefits minority of patients, underscoring the importance discovering reliable biomarkers can be used screen for beneficiaries and ultimately reduce risk overtreatment. Our comprehensive review focuses on latest advancements predictive ICI therapy, particularly emphasizing those enhance efficacy programmed cell death protein 1 (PD-1)/programmed death-ligand (PD-L1) inhibitors cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapies. We explore derived from various sources, including tumor cells, microenvironment (TIME), body fluids, gut microbes, metabolites. Among them, cells-derived include mutational burden (TMB) biomarker, neoantigen (TNB) microsatellite instability (MSI) PD-L1 expression mutated gene pathways, epigenetic biomarkers. TIME-derived landscape TIME biomarkers, inhibitory checkpoints repertoire also discuss techniques detect assess these detailing their respective datasets, strengths, weaknesses, evaluative metrics. Furthermore, we present computer models predicting response therapy. The knowledge-based mechanistic data-based machine learning (ML) models. are pharmacokinetic/pharmacodynamic (PK/PD) models, partial differential equation (PDE) signal networks-based quantitative systems pharmacology (QSP) agent-based (ABMs). ML linear regression logistic support vector (SVM)/random forest/extra trees/k-nearest neighbors (KNN) artificial neural network (ANN) deep Additionally, there hybrid biology ML. summarized details outlining datasets they utilize, evaluation methods/metrics, strengths limitations. By summarizing major advances research therapeutic effect utility ICI, aim assist researchers choosing appropriate or exploration help clinicians conduct precision medicine by selecting best

Language: Английский

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Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(3), P. e007364 - e007364

Published: March 1, 2024

Background Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab a monoclonal antibody agonist that binds CD137 receptors expressed on T cells. Here, we report two studies evaluated urelumab in combination with cetuximab or nivolumab patients select, advanced solid tumors. Methods CA186-018: Patients metastatic colorectal squamous cell carcinoma of the head neck (SCCHN) were treated dose-evaluation phase 0.1 mg/kg (urelumab-0.1) every 3 weeks (Q3W)+cetuximab 250 mg/m 2 (cetuximab-250) weekly; dose-expansion 8 mg flat dose (urelumab-8) Q3W+cetuximab-250 weekly. CA186-107: The dose-escalation included previously tumors (or treatment-naive melanoma); received (urelumab-3) urelumab-8 4 weeks+nivolumab (nivolumab-3) 240 (nivolumab-240) weeks. In expansion phase, melanoma, non-small lung cancer, SCCHN urelumab-8+nivolumab-240. Primary endpoints safety tolerability, secondary endpoint efficacy assessments. Results 66 study treatment. most frequent treatment-related adverse events (TRAEs) fatigue (75%; n=3) urelumab-0.1+cetuximab-250 dermatitis (45%; n=28) urelumab-8+cetuximab-250. Three (5%) discontinued due TRAE(s) (with urelumab-8+cetuximab-250). One patient had partial response (objective rate (ORR) 5%, 134 Fatigue was common TRAE (32%; n=2 urelumab-3+nivolumab-3; n=1 urelumab-8+nivolumab-3; n=40 urelumab-8+nivolumab-240). Nine (7%) (n=1 n=8 melanoma naive anti-PD-1 therapy exhibited highest ORR (49%; n=21 Intratumoral gene expression immune-related pathways (CD3, CD8, CXCL9, GZMB) increased treatment urelumab+nivolumab. Conclusions Although addition at these doses tolerable, preliminary rates did not indicate an evident additive benefit. Nevertheless, positive pharmacodynamics effects observed high warrant further investigation other anti-CD137 cancer. Trial registration numbers NCT02110082 ; NCT02253992 .

Language: Английский

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