Natural killer cells: a promising immunotherapy for cancer

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: May 23, 2022

Abstract As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK can rapidly kill multiple adjacent cancer through non-MHC-restrictive effects. Although tumors may develop resistance mechanisms to endogenous cell attack, in vitro activation, expansion, and genetic modification greatly enhance their anti-tumor activity give them the ability overcome drug resistance. Some these approaches been translated into clinical applications, trials infusion patients with hematological malignancies solid thus far yielded many encouraging results. CAR-T exhibited great success treating malignancies, but drawbacks include high manufacturing costs potentially fatal toxicity, such cytokine release syndrome. To issues, CAR-NK were generated engineering demonstrated significant responses lower adverse effects compared therapy. In this review, we summarize recent advances focusing on biology function, types therapy, future perspectives

Language: Английский

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Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4562 - 4562

Published: Sept. 20, 2022

Lung cancer is one of the leading causes cancer-related deaths worldwide with a 5-year survival rate less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains major obstacle effectiveness long-term treatment, eventually insensitivity, poor progression-free survival, disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations microenvironment, several other cellular molecular alterations. A better understanding these crucial for targeting factors involved resistance, establishing novel antitumor targets, developing strategies resensitize cells towards treatment. In this review, we summarize diverse driving radiotherapy, immunotherapy, promising help overcome resistance.

Language: Английский

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Personalized neoantigen vaccine enhances the therapeutic efficacy of bevacizumab and anti-PD-1 antibody in advanced non-small cell lung cancer

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(2)

Published: Jan. 27, 2024

Abstract Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, personalized tumor DNA mutations, could elicit specific T infiltration into site, exerting potent anti-tumor efficacy. Here, we evaluated feasibility safety new antitumor strategy by adding neoantigen vaccine regimen bevacizumab anti-PD-1 antibody. Firstly, 7 novel immunogenic peptides were identified developed for (LLCvac), which can strong response in vivo. Then, orthotopic model, LLCvac further combining antibody exerted stronger effect, exhibiting significant decrease volume without obvious toxicity. Furthermore, microenvironment assessment also showed that proportion neoantigen-specific cells blood be induced dramatically therapy. And large amount Ki67-positive CD8 + found tissues, infiltrated tissues effectively kill expressing neoantigens. Overall, these results suggested this therapy safely induce robust efficacy, serving as an effective chemotherapy-free NSCLC treatment.

Language: Английский

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The role of epithelial–mesenchymal transition-regulating transcription factors in anti-cancer drug resistance

Archives of Pharmacal Research, Journal Year: 2021, Volume and Issue: 44(3), P. 281 - 292

Published: March 1, 2021

Abstract The complex orchestration of gene expression that mediates the transition epithelial cells into mesenchymal is implicated in cancer development and metastasis. As primary regulator process, epithelial-mesenchymal transition-regulating transcription factors (EMT-TFs) play key roles They are also highlighted recent preclinical studies on resistance to therapy. This review describes role three main EMT-TFs, including Snail, Twist1, zinc-finger E homeobox-binding 1 (ZEB1), relating drug current possible approaches for future challenges targeting EMT-TFs.

Language: Английский

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Current opinion on the pharmacogenomics of paclitaxel-induced toxicity

Expert Opinion on Drug Metabolism & Toxicology, Journal Year: 2021, Volume and Issue: 17(7), P. 785 - 801

Published: June 15, 2021

Introduction: Paclitaxel is a microtubule stabilizer that currently one of the most utilized chemotherapeutic agents. Its efficacy in breast, uterine, lung and other neoplasms made its safety profile enhancement subject great interest. Neurotoxicity common paclitaxel-associated toxicities. In addition, hypersensitivity reactions, hematological, gastrointestinal, cardiac toxicities are all encountered.Areas covered: The current review explores paclitaxel-induced mechanisms risk factors. Studies investigating these pharmacogenomic biomarkers reviewed summarized. There limited margin consistency between retrieved associations. Variants genes related to neuro-sensitivity promising candidates for future studies.Expert opinion: Genome-wide association studies highlighted multiple-candidate relevant neuro-sensitivity. Most identified paclitaxel-neurotoxicity candidate derived from congenital neuropathy diabetic-induced neurotoxicity pathways. Future should explore sets while considering multifactorial nature neurotoxicity. absence certain paclitaxel-toxicity biomarkers, research avoid earlier studies' caveats. Genes paclitaxel's pharmacokinetic pathways could not provide consistent results any associated need dig deeper into toxicity-development personal vulnerability factors, rather than targeting only suspected affect drug exposure.

Language: Английский

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Tumor-associated macrophages in non-small-cell lung cancer: From treatment resistance mechanisms to therapeutic targets

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 196, P. 104284 - 104284

Published: Feb. 2, 2024

Non-small cell lung cancer (NSCLC) remains one of the leading causes cancer-related deaths worldwide. Different treatment approaches are typically employed based on stage NSCLC. Common clinical methods include surgical resection, drug therapy, and radiation therapy. However, with introduction utilization immune checkpoint inhibitors, has entered a new era, completely revolutionizing landscape for various cancers significantly improving overall patient survival. Concurrently, resistance often poses critical challenge, many patients experiencing disease progression following an initial response due to resistance. Increasing evidence suggests that tumor microenvironment (TME) plays pivotal role in Tumor-associated macrophages (TAMs) within TME can promote NSCLC by secreting cytokines activating signaling pathways, interacting other cells. Therefore, this article will focus elucidating key mechanisms TAMs analyze how targeting reduce levels NSCLC, providing comprehensive understanding principles overcome

Language: Английский

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Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Nov. 29, 2021

Gastric cancer (GC) is one of the most common malignant tumors digestive systems worldwide, with high recurrence and mortality. Chemotherapy still standard treatment option for GC can effectively improve survival life quality patients. However, emergence drug resistance, clinical application chemotherapeutic agents has been seriously restricted in Although mechanisms resistance have broadly investigated, they are largely unknown. MicroRNAs (miRNAs) a large group small non-coding RNAs (ncRNAs) widely involved occurrence progression many types, including GC. An increasing amount evidence suggests that miRNAs may play crucial roles development by regulating some resistance-related proteins as well gene expression. Some also exhibit great potential novel biomarkers predicting response to chemotherapy therapeutic targets In this review, we systematically summarize recent advances focus on their molecular progression. We highlight

Language: Английский

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Long-term comparative efficacy and safety of nivolumab plus ipilimumab relative to other first-line therapies for advanced non-small-cell lung cancer: A systematic literature review and network meta-analysis

Lung Cancer, Journal Year: 2023, Volume and Issue: 177, P. 11 - 20

Published: Jan. 11, 2023

To quantify the long-term comparative efficacy and safety of nivolumab in combination with ipilimumab (NIVO + IPI) relative to other immunotherapy (IO)-based regimens chemotherapy patients first-line advanced non-small cell lung cancer (aNSCLC).Phase 3 randomized controlled-trials (RCTs) minimum 3-year follow-up evaluating IO-based approved for aNSCLC were identified via systematic literature review. Analytic populations defined by levels PD-L1 expression histology. Due presence proportional hazards violations, time-varying hazard ratios (HRs) overall survival (OS) progression-free (PFS) estimated Bayesian fractional polynomial network meta-analysis. For endpoints, odds (ORs) using indirect treatment comparisons (ITCs).CheckMate 227, KEYNOTE-189, KEYNOTE-407, KEYNOTE-024, KEYNOTE-042, IMpower150 included base case analysis. OS PFS, HRs NIVO IPI trended downward over time across analytic populations. The 36-month versus comparators were: 0.69 (95 % credible interval: 0.47, 1.00) pembrolizumab 0.65 (0.45, 0.93) atezolizumab bevacizumab non-squamous all-comers population; 0.73 (0.53, 1.02) squamous 1.05 (0.83, 1.32) mixed histology ≥ 50 population. HR point estimates ranged from 0.46 0.85 (only statistically significant [0.31, 0.69]). Adverse events (AEs) leading discontinuation not significantly different between chemotherapy, nor monotherapy, although treatment-related grade AEs higher than monotherapy (OR = 2.21 [1.30, 3.75]).This study indicates trends towards benefit compared combinations, manageable toxicities.

Language: Английский

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Nanomedicine-based adjuvant therapy: a promising solution for lung cancer

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 6, 2023

Abstract Lung cancer has been the leading cause of cancer-related deaths worldwide for decades. Despite increasing understanding underlying disease mechanisms, prognosis still remains poor many patients. Novel adjuvant therapies have emerged as a promising treatment method to augment conventional methods and boost therapeutic effects primary therapies. Adjuvant therapy based on nanomedicine gained considerable interest supporting enhancing traditional therapies, such chemotherapy, immunotherapy, radiotherapy, due tunable physicochemical features ease synthetic design nanomaterials. In addition, can provide protective against other by reducing adverse side through precise targeting. Therefore, nanomedicine-based extensively employed in wide range preclinical clinical treatments overcome drawbacks this review, we mainly discuss recent advances lung highlight their functions improving outcome which may inspire new ideas advanced stimulate research efforts around topic. Graphical

Language: Английский

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Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3836 - 3836

Published: July 28, 2023

Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory conventional diagnostic chemotherapeutics due their limited targetability, specificity, solubility, side effects. The inherent ability of each cancer evolve through various genetic epigenetic transformations metabolic reprogramming underlies limitations. Though tumor microenvironments (TMEs) quite well understood some cancers, microenvironment differs from other internal perturbations skew thereby impeding development appropriate diagnostics, drugs, vaccines, therapies. associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation resistant niches progression, a thorough understanding crucial However, this remains missing element theranostics, necessitating modalities that can be adapted for diagnostics therapeutics. In challenging scenario, nanomaterials modular platforms TME achieving successful theranostics. Several nanoscale particles have been successfully researched animal models, few reached clinical trials, achieved Nanoparticles exhibit intrinsic capability interact with diverse biomolecules modulate functions. Furthermore, nanoparticles functionalized receptors, modulators, drugs facilitate specific targeting reduced toxicity. This review discusses current different theranostic nanosystems, synthesis, functionalization, targetability modulation bioenergetics, microenvironment. We highlight potential nanosystems enhanced chemotherapeutic success emphasizing questions remain unanswered.

Language: Английский

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