Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Language: Английский

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Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Dec. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Language: Английский

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The role of lipids in cancer progression and metastasis

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(11), P. 1675 - 1699

Published: Oct. 18, 2022

Language: Английский

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Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective

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

Published: Sept. 17, 2022

Abstract Protein tyrosine kinases (PTKs) are a class of proteins with kinase activity that phosphorylate residues critical molecules in signaling pathways. Their basal function is essential for maintaining normal cell growth and differentiation. However, aberrant activation PTKs caused by various factors can deviate from the expected trajectory to an abnormal state, leading carcinogenesis. Inhibiting PTK could inhibit tumor growth. Therefore, inhibitors (TKIs), target-specific PTKs, have been used treating malignant tumors play significant role targeted therapy cancer. Currently, drug resistance main reason limiting TKIs efficacy The increasing studies indicated microenvironment, death resistance, metabolism, epigenetic modification metabolism were deeply involved development TKI besides PTK-related pathways gene mutations. Accordingly, it great significance study underlying mechanisms find solutions reverse improving Herein, we reviewed potential approaches overcome aiming provide theoretical basis TKIs.

Language: Английский

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Targeting ROS in cancer: rationale and strategies

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(8), P. 583 - 606

Published: July 9, 2024

Language: Английский

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Inhibition of ferroptosis and iron accumulation alleviates pulmonary fibrosis in a bleomycin model

Redox Biology, Journal Year: 2022, Volume and Issue: 57, P. 102509 - 102509

Published: Oct. 18, 2022

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by excessive proliferation of fibroblasts and accumulation extracellular matrix (ECM). Ferroptosis novel form cell death the lethal iron lipid peroxidation, which associated with many diseases. Our study addressed potential role played ferroptosis in progression fibrosis. We found that inducers injury, namely, bleomycin (BLM) lipopolysaccharide (LPS), induced lung epithelial cells. Both inhibitor liproxstatin-1 (Lip-1) chelator deferoxamine (DFO) alleviated symptoms or LPS. TGF-β stimulation upregulated expression transferrin receptor protein 1 (TFRC) human fibroblast line (MRC-5) mouse primary fibroblasts, resulting increased intracellular Fe2+, promoted transformation into myofibroblasts. Mechanistically, enhanced nuclear localization transcriptional coactivator tafazzin (TAZ), combined transcription factor TEA domain (TEAD)-4 to promote TFRC. In addition, elevated Fe2+ failed induce might be related regulation export metabolism. Finally, we specifically knocked out TFRC mice, compared those control were reduced knockout mice after induction. Collectively, these findings suggest therapeutic inhibitors chelators treating

Language: Английский

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Stearoyl coenzyme A desaturase-1: multitasker in cancer, metabolism, and ferroptosis

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(6), P. 480 - 489

Published: April 6, 2023

Cancer progression is a highly balanced process and maintained by sequence of finely tuned metabolic pathways. Stearoyl coenzyme A desaturase-1 (SCD1), the fatty enzyme that converts saturated acids into monounsaturated acids, critical modulator acid pathway. SCD1 expression associated with poor prognosis in several cancer types. triggers an iron-dependent cell death called ferroptosis elevated levels protect cells against ferroptosis. Pharmacological inhibition as monotherapy combination chemotherapeutic agents shows promising antitumor potential preclinical models. In this review, we summarize role SCD progression, survival, discuss strategies to exploit future clinical trials.

Language: Английский

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Lipid-associated macrophages in the tumor-adipose microenvironment facilitate breast cancer progression

OncoImmunology, Journal Year: 2022, Volume and Issue: 11(1)

Published: June 8, 2022

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are most abundant immune cell type within TAME, although their diversity in TAME not clear. We first reveal infiltration M2-like macrophages associated with poor survival breast cancer. To explore lipid-associated alterations we also detected levels FFAs transporters including acid binding proteins (FABPs) and transport protein 1 (FATP1). results indicated expression tightly linked to function predicts impact on macrophages, performed single-cell RNA sequencing (scRNA-seq) spatial transcriptomics. Consequently, identified special subpopulation defined (LAMs), highly expressed macrophage markers (CD163, SPP1 C1QC), genes involved metabolism (FABP3, FABP4, FABP5, LPL LIPA) some receptors (LGALS3 TREM2). Functionally, LAMs were canonical functional signature accumulation enhancing phagocytosis, they mostly distributed junctional regions. Finally, allograft cancer mouse models confirmed depletion synergizes antitumorigenic effects anti-PD1 therapy. In summary, novel subtype has unique features clinical outcomes.

Language: Английский

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Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1–Wnt/β‐catenin–TFE3 feedback loop signalling

Clinical and Translational Medicine, Journal Year: 2022, Volume and Issue: 12(4)

Published: April 1, 2022

Language: Английский

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SGLT-2 Inhibitors in Cancer Treatment—Mechanisms of Action and Emerging New Perspectives

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5811 - 5811

Published: Nov. 25, 2022

A new group of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT-2 inhibitors), have recently been shown to anticancer effects and their expression has confirmed in many cancer cell lines. Given the metabolic reprogramming these cells a glucose-based model, ability SGLT-2 block glucose uptake by appears be an attractive therapeutic approach. In addition tumour cells, SGLT-2s are only found proximal tubules kidneys. Furthermore, as numerous clinical trials shown, use is well-tolerated safe patients with diabetes and/or heart failure. vitro culture studies preclinical vivo that exhibit antiproliferative on certain types cancer. However, mechanisms this action remain unclear. Even those which present, there sometimes SGLT-2-independent mechanism drugs. This article presents current state knowledge potential possible future application oncology.

Language: Английский

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