The impact of hypoxia on tumor-mediated bypassing anti-PD-(L)1 therapy

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114646 - 114646

Published: April 1, 2023

Extending the durability of response is current focus in cancer immunotherapy with immune checkpoint inhibitors (ICIs). However, factors like non-immunogenic tumor microenvironment (TME) along aberrant angiogenesis and dysregulated metabolic systems are negative contributors. Hypoxia a key TME condition critical promoter hallmarks. It acts on non-immune cells within order for promoting evasion therapy resistance. Extreme hypoxia major resistance to programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. inducible factor-1 (HIF-1) as mediator anti-PD-(L)1. Targeting or HIF-1 can thus be an effective strategy reinvigoration cellular immunity against cancer. Among various strategies presented so far, over vascular normalization, which approach highly reducing rate hypoxia, increasing drug delivery into area, boosting efficacy

Language: Английский

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Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10859 - 10859

Published: June 29, 2023

The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because recurrent episodes in the majority (~70%) patients with advanced OC. Clinical trials have shown only a modest (10-15%) response OC individuals to based on immune checkpoint inhibitors (ICIs). resistance therapy caused by various factors, heterogeneity, low density tumor-infiltrating lymphocytes (TILs), non-cellular cellular interactions tumor microenvironment (TME), as well network microRNA regulating pathways. Moreover, ICIs are most efficient tumors that marked high microsatellite instability mutation burden, which rare among patients. great challenge ICI implementation connected distinguishing hyper-, pseudo-, real progression disease. understanding immunological, molecular, genetic mechanisms crucial selecting group whom personalized would be beneficial. In this review, we summarize current knowledge about selected factors inducing discuss future directions ICI-based immunotherapy development for

Language: Английский

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Anti-PD-1/PD-L1 therapy for colorectal cancer: Clinical implications and future considerations

Translational Oncology, Journal Year: 2023, Volume and Issue: 40, P. 101851 - 101851

Published: Dec. 1, 2023

Colorectal cancer (CRC) is the third most prevalent in world. The PD-1/PD-L1 pathway plays a crucial role modulating immune response to cancer, and PD-L1 expression has been observed tumor cells within microenvironment of CRC. Thus, immunotherapy drugs, specifically checkpoint inhibitors, have developed target signaling pathway, thereby inhibiting interaction between PD-1 restoring T-cell function cells. However, emergence resistance mechanisms can reduce efficacy these treatments. To counter this, monoclonal antibodies (mAbs) used improve CRC mAbs such as nivolumab pembrolizumab are currently approved for treatment. These impede receptors, including PD-1/PD-L1, their combination therapy shows promise treatment advanced This review presents concise overview use blockade therapeutic strategy using therapies. Additionally, this article outlines an suppressor well potential advantages administering inflammatory agents Finally, analyzes outcomes clinical trials examine challenges anti-PD-1/PD-L1 resistance.

Language: Английский

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IL-2 based cancer immunotherapies: an evolving paradigm

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

Published: July 24, 2024

Discovered over 4 decades ago in the supernatants of activated T cells, interleukin-2 (IL-2) is a potent pleiotropic cytokine involved regulation immune responses. It required for effector cell expansion and differentiation as well peripheral tolerance induced by regulatory cells. High-dose IL-2 treatment was first FDA-approved immunotherapy renal carcinoma melanoma, achieving single agent complete durable responses, albeit only small proportion patients. The therapeutic potential wild type clinically limited its short half-life severe vascular toxicity. Moreover, activation cells terminal on pose additional restrictions. To overcome toxicity order to realize full patients, several novel engineering strategies are being developed based cancer has emerged burgeoning field clinical experimental research. In addition, combination with PD-1/L1 pathway blockade shows vastly improved anti-tumor efficacy either monotherapy preclinical tumor models. this review we discuss biological characteristics receptors, limiting toxicities We also explore efforts aimed at developing safer therapies harness cytokine.

Language: Английский

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Phytochemical synergies in BK002: advanced molecular docking insights for targeted prostate cancer therapy

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Achyranthes japonica (Miq.) Nakai (AJN) and Melandrium firmum (Siebold Zucc.) Rohrb. (MFR) are medicinal plants recognized for their bioactive phytochemicals, including ecdysteroids, anthraquinones, flavonoids. This study investigates the anticancer properties of key constituents these plants, focusing on BK002 formulation, a novel combination AJN MFR. Specifically, research employs advanced molecular docking in silico analyses to assess interactions compounds ecdysterone, inokosterone, 20-hydroxyecdysone (20-HE) with prostate cancer-related network proteins, 5α-reductase, CYP17, DNMT1, Dicer, PD-1, PD-L1. Molecular techniques were applied evaluate binding affinities contributions against cancer-hub targets. The primary focus was enzymes like 5α-reductase which central androgen biosynthesis, as well proteins such DNA methyltransferase 1 (DNMT1), programmed death-1 (PD-1), death ligand-1 (PD-L1). Based data from cancer patients, target networks identified, followed by analysis components BK002.In assessments conducted safety profiles compounds, providing insights into therapeutic potential. studies revealed that 20-hydroxyecdysonec demonstrated strong critical contributing potential reduction androgenic activity. These also exhibited significant inhibitory PD-L1, suggesting capacity interfere oncogenic immune evasion pathways. Ecdysterone, have ability pathways, favorable affinity further underscore agents cancer. findings provide rationale preclinical clinical investigations, supporting integration regimens aimed at modulating tumor progression responses.

Language: Английский

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