Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment DOI Creative Commons
Fusheng Zhang,

Junchen Guo,

Shengmiao Yu

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(9), P. 929 - 966

Published: July 12, 2024

Abstract The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features TME include metabolic reprogramming, hypoxia, chronic inflammation, immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes mediate intercellular information exchange play a role in dynamic evolution TME. Specifically, hypoxic adaptation, dysregulation, phenotypic shifts immune cells regulated by cellular senescence synergistically contribute to development an immunosuppressive thereby promoting progression events. This review provides comprehensive summary processes which regulates tumor‐adapted TME, with focus on complex underlying relationship between changes biological functions cells. available findings components collectively potential applications challenges targeted senescence‐based combination therapies clinical settings are further discussed within context advancing senescence‐related research.

Language: Английский

Targeting triple negative breast cancer stem cells using nanocarriers DOI Creative Commons
Nagasen Dasari, Girijasankar Guntuku, Sai Kiran S. S. Pindiprolu

et al.

Discover Nano, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 7, 2024

Abstract Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, treatment responses. Categorization of based on the presence or absence estrogen receptor (ER), progesterone (PR), human epidermal growth factor 2 (HER2), leading to such as luminal A, B, HER2-positive, triple-negative breast (TNBC). TNBC, comprising around 20% all cancers, lacks expression ER, PR, HER2 receptors, rendering it unresponsive targeted therapies presenting significant challenges in treatment. TNBC associated with aggressive behavior, high rates recurrence, resistance chemotherapy. Tumor initiation, progression, are attributed stem cells (BCSCs), which possess self-renewal, differentiation, tumorigenic potential. Surface markers, self-renewal pathways (Notch, Wnt, Hedgehog signaling), apoptotic protein (Bcl-2), angiogenesis inhibition (VEGF inhibitors), immune modulation (cytokines, checkpoint inhibitors) among key targets discussed this review. However, targeting BCSC subpopulation presents challenges, including off-target effects, low solubility, bioavailability anti-BCSC agents. Nanoparticle-based offer promising approach target cellular processes implicated survival BSCS TNBC. In review, we explore nanocarrier-based approaches for BCSCs aiming overcome these improve outcomes patients. These nanoparticle-based therapeutic strategies hold promise addressing gap delivering while minimizing systemic toxicity enhancing efficacy. Graphical abstract

Language: Английский

Citations

17
The role of cellular senescence in neurodegenerative diseases DOI Creative Commons
Yating Wang, Kamil Kuča, You Li

et al.

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(8), P. 2393 - 2408

Published: May 15, 2024

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of hallmarks (p16 p21) elevated β-galactosidase activity in vitro vivo ND models. These contribute to the deposition β-amyloid tau-protein tangles. Selective clearance SASP regulation by inhibiting p38/mitogen-activated protein kinase nuclear factor kappa B signaling attenuate load prevent tangle deposition, thereby improving cognitive performance AD mouse In addition, telomere shortening, a biomarker, is associated with increased risks. Telomere dysfunction causes senescence, stimulating tumor necrosis factor-α, IL-1β secretions. The forced telomerase activators prevents yielding considerable neuroprotective effects. This review elucidates mechanism pathogenesis, suggesting strategies eliminate or restore normal phenotype for treating such diseases.

Language: Английский

Citations

17
Prostaglandin E2 in the Tumor Microenvironment, a Convoluted Affair Mediated by EP Receptors 2 and 4 DOI Creative Commons
Ana Santiso, Ákos Heinemann, Julia Kargl

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 388 - 413

Published: March 4, 2024

Abstract

The involvement of the prostaglandin E2 (PGE2) system in cancer progression has long been recognized. PGE2 functions as an autocrine and paracrine signaling molecule with pleiotropic effects human body. High levels intratumoral overexpression key metabolic enzymes have observed suggested to contribute tumor progression. This claimed for different types solid tumors, including, but not limited to, lung, breast, colon cancer. direct on cells angiogenesis that are known promote development. However, one main mechanisms behind driving cancerogenesis is currently thought be anchored suppressed antitumor immunity, thus providing possible therapeutic targets used immunotherapies. EP2 EP4, two receptors PGE2, emerging being most relevant this purpose. review aims summarize roles immune its within microenvironment.

Significance Statement

Prostaglandin a Its presence tumors repeatedly associated disease Elucidation immunological components microenvironment highlighted potential receptor antagonists treatment, particularly combination checkpoint inhibitor therapeutics. Adjuvant treatment could increase response rates efficacy immune-based therapies.

Language: Английский

Citations

16
Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment DOI Creative Commons

Shijiao Zhi,

Chen Chen, Hanlin Huang

et al.

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

Published: May 10, 2024

Globally, breast cancer stands as the most prevalent form of among women. The tumor microenvironment often exhibits hypoxia. Hypoxia-inducible factor 1-alpha, a transcription factor, is found to be overexpressed and activated in cancer, playing pivotal role anoxic by mediating series reactions. 1-alpha involved regulating downstream pathways target genes, which are crucial hypoxic conditions, including glycolysis, angiogenesis, metastasis. These processes significantly contribute progression managing cancer-related activities linked invasion, metastasis, immune evasion, drug resistance, resulting poor prognosis for patients. Consequently, there significant interest potential therapy. Presently, research on drugs targeting predominantly preclinical phase, highlighting need an in-depth understanding HIF-1α its regulatory pathway. It anticipated that future will see introduction effective inhibitors into clinical trials, offering new hope Therefore, this review focuses structure function HIF-1α, advancing strategies combat HIF-1α-dependent underlining therapeutic potential.

Language: Английский

Citations

16
Tumor microenvironment targeted nano-drug delivery systems for multidrug resistant tumor therapy DOI Creative Commons

Xinyue Shao,

Xiaoling Zhao, Binghao Wang

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1689 - 1714

Published: Jan. 2, 2025

In recent years, nano-drug delivery systems (Nano-DDS) that target the tumor microenvironment (TME) to overcome multidrug resistance (MDR) have become a research hotspot in field of cancer therapy. By precisely targeting TME and regulating its unique pathological features, such as hypoxia, weakly acidic pH, abnormally expressed proteins, etc., these Nano-DDS enable effective therapeutic agents reversal MDR. This scientific community is increasing investment development diversified exploring their anti-drug potential. Therefore, it particularly important conduct comprehensive review progress TME-targeted years. After brief introduction MDR, design principle structure liposomes, polymer micelles inorganic nanocarriers are focused on, characteristics described. It also demonstrates how break through MDR treatment various mechanisms, discusses synthetic innovation, results overcoming mechanisms. The was concluded with deliberations on key challenges future outlooks

Language: Английский

Citations

3
The molecular code of kidney cancer: A path of discovery for gene mutation and precision therapy DOI Creative Commons
Deqian Xie,

Guandu Li,

Zhonghua Zheng

et al.

Molecular Aspects of Medicine, Journal Year: 2025, Volume and Issue: 101, P. 101335 - 101335

Published: Jan. 1, 2025

Renal cell carcinoma (RCC) is a malignant tumor with highly heterogeneous and complex molecular mechanisms. Through systematic analysis of TCGA, COSMIC other databases, 24 mutated genes closely related to RCC were screened, including VHL, PBRM1, BAP1 SETD2, which play key roles in signaling pathway transduction, chromatin remodeling DNA repair. The PI3K/AKT/mTOR particularly important the pathogenesis RCC. Mutations such as PIK3CA, MTOR PTEN are associated metabolic abnormalities proliferation. Clinically, mTOR inhibitors VEGF-targeted drugs have shown significant efficacy personalized therapy. Abnormal regulation reprogramming, especially glycolysis glutamine pathways, provides cells continuous energy supply survival advantages, GLS1 promising results preclinical studies. This paper also explores potential immune checkpoint combination targeted drugs, well application nanotechnology drug delivery In addition, unique mechanisms revealed individualized therapeutic strategies explored for specific subtypes TFE3, TFEB rearrangement type SDHB mutant type. review summarizes common gene mutations their mechanisms, emphasizes diagnosis, treatment prognosis, looks forward prospects multi-pathway therapy, immunotherapy treatment, providing theoretical support clinical guidance new development.

Language: Английский

Citations

2
Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis DOI
Hardeep Singh Tuli, Jagjit Kaur,

Kanupriya Vashishth

et al.

Archives of Toxicology, Journal Year: 2022, Volume and Issue: 97(1), P. 103 - 120

Published: Nov. 28, 2022

Language: Английский

Citations

57
Natural flavonoids exhibit potent anticancer activity by targeting microRNAs in cancer: A signature step hinting towards clinical perfection DOI Creative Commons
Hardeep Singh Tuli, Vivek Kumar Garg,

Sakshi Bhushan

et al.

Translational Oncology, Journal Year: 2022, Volume and Issue: 27, P. 101596 - 101596

Published: Dec. 5, 2022

Cancer prevalence and its rate of incidence are constantly rising since the past few decades. Owing to toxicity present-day antineoplastic drugs, it is imperative explore safer more effective molecules combat and/or prevent this dreaded disease. Flavonoids, a class polyphenols, have exhibited multifaceted implications against several diseases including cancer, without showing significant towards normal cells. Shredded pieces evidence suggest that flavonoids can enhance drug sensitivity suppress proliferation, metastasis, angiogenesis cancer cells by modulating oncogenic or oncosuppressor microRNAs (miRNAs, miRs). They play pivotal roles in regulation various biological pathological processes, cancers. In present review, structure, chemistry miR targeting efficacy quercetin, luteolin, silibinin, genistein, epigallocatechin gallate, cyanidin types comprehensively discussed. miRs considered as next-generation medicine recent times, their naturally occurring could be deemed signature step. We anticipate our compilations related miRNA-mediated might catapult clinical investigations affirmation future.

Language: Английский

Citations

47
Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy DOI Open Access
Qi Liu,

Chengcheng Guan,

Cui Liu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113861 - 113861

Published: Oct. 10, 2022

Triple-negative breast cancer (TNBC) is a subtype of that highly aggressive and hypoxic compared with other subtypes. The role hypoxia inducible factor 1α (HIF-1α) as key transcription in oncogenic processes has been extensively studied. Recently, it shown HIF-1α regulates the complex biological TNBC, such glycolysis, angiogenesis, invasion metastasis, stem cells (BCSCs) enrichment, immune escape, to promote TNBC survival development through activation downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, signaling regulatory networks, epigenetic regulators are involved upstream expression HIF-1α. However, further studies needed determine potential future directions targeting TNBC. This article discusses We also explored mechanism by which drives progression. significance for immunotherapy, chemotherapy, anti-angiogenic therapy, photodynamic therapy discussed. intrinsic mechanism, existing problems

Language: Английский

Citations

45
Polysaccharide‐Based Stimulus‐Responsive Nanomedicines for Combination Cancer Immunotherapy DOI
Qiuxia Li, Xing Liu, Chunmei Yan

et al.

Small, Journal Year: 2023, Volume and Issue: 19(23)

Published: March 8, 2023

Cancer immunotherapy is a promising antitumor approach, whereas nontherapeutic side effects, tumor microenvironment (TME) intricacy, and low immunogenicity limit its therapeutic efficacy. In recent years, combination with other therapies has been proven to considerably increase However, achieving codelivery of the drugs site remains major challenge. Stimulus-responsive nanodelivery systems show controlled drug delivery precise release. Polysaccharides, family potential biomaterials, are widely used in development stimulus-responsive nanomedicines due their unique physicochemical properties, biocompatibility, modifiability. Here, activity polysaccharides several combined strategies (e.g., chemotherapy, photodynamic therapy, or photothermal therapy) summarized. More importantly, progress polysaccharide-based for cancer discussed, focus on construction nanomedicine, targeted delivery, release, enhanced effects. Finally, limitations application prospects this new field discussed.

Language: Английский

Citations

37