Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer

BioFactors ◽  
2021 ◽  
Author(s):  
Leila Kooshki ◽  
Parisa Mahdavi ◽  
Sajad Fakhri ◽  
Esra Küpeli Akkol ◽  
Haroon Khan
Keyword(s):  
Natural Products ◽  
Tumor Microenvironment ◽  
Lactate Metabolism ◽  
Promising Strategy

pH-responsive size-shrinkable mesoporous silica-based nanocarrier for improved tumor penetration and therapeutic efficacy

Nanoscale ◽  
2022 ◽  
Author(s):  
Yongju He ◽  
Xingyu Fan ◽  
Xiaozan Wu ◽  
Taishun Hu ◽  
Fangfang Zhou ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Mesoporous Silica ◽  
Therapeutic Efficacy ◽  
Anticancer Therapy ◽  
Major Obstacle ◽  
Drug Penetration ◽  
Ph Responsive ◽  
Tumor Penetration ◽  
Promising Strategy

Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across...

scholarly journals Targeting regulatory T cells for immunotherapy in melanoma

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Lili Huang ◽  
Yeye Guo ◽  
Shujing Liu ◽  
Huaishan Wang ◽  
Jinjin Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Efficacy ◽  
Patient Survival ◽  
Therapeutic Antibodies ◽  
Promising Strategy ◽  
Fine Tune

AbstractRegulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor. Tregs are frequently accumulated in melanoma and the ratio of CD8+ T cells versus Tregs in the melanoma is predictive for patient survival. Hence, depletion of Tregs is a promising strategy for the enhancement of anti-melanoma immunity. Many recent studies are aimed to target Tregs in melanoma. Distinguishing Tregs from other immune cells and understanding the function of different subsets of Tregs may contribute to better therapeutic efficacy. Depletion of functional Tregs from the tumor microenvironment has been tested to induce clinically relevant immune responses against melanomas. However, the lack of Treg specific therapeutic antibodies or Treg specific depleting strategies is a big hurdle that is yet to be overcome. Additional studies to fine-tune currently available therapies and more agents that specifically and selectively target tumor infiltrating Tregs in melanoma are urgently needed.

Modulation of tumor microenvironment by chemopreventive natural products

2017 ◽  
Vol 1401 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Sin-Aye Park ◽  
Young-Joon Surh
Keyword(s):  
Natural Products ◽  
Tumor Microenvironment

scholarly journals Macrophages in Osteosarcoma Immune Microenvironment: Implications for Immunotherapy

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhong-Wei Luo ◽  
Pan-Pan Liu ◽  
Zhen-Xing Wang ◽  
Chun-Yuan Chen ◽  
Hui Xie
Keyword(s):  
Overall Survival ◽  
Tumor Microenvironment ◽  
Bone Tumor ◽  
Immune Cells ◽  
Therapeutic Approaches ◽  
Immune Microenvironment ◽  
Primary Bone Tumor ◽  
Promising Strategy ◽  
Primary Bone ◽  
Malignant Primary Bone Tumor

Osteosarcoma is a malignant primary bone tumor commonly occurring in children and adolescents. The treatment of local osteosarcoma is mainly based on surgical resection and chemotherapy, whereas the improvement of overall survival remains stagnant, especially in recurrent or metastatic cases. Tumor microenvironment (TME) is closely related to the occurrence and development of tumors, and macrophages are among the most abundant immune cells in the TME. Due to their vital roles in tumor progression, macrophages have gained increasing attention as the new target of tumor immunotherapy. In this review, we present a brief overview of macrophages in the TME and highlight the clinical significance of macrophages and their roles in the initiation and progression of osteosarcoma. Finally, we summarize the therapeutic approaches targeting macrophage, which represent a promising strategy in osteosarcoma therapies.

scholarly journals A Novel Lactate Metabolism-Related Gene Signature for Predicting Clinical Outcome and Tumor Microenvironment in Hepatocellular Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Yue Li ◽  
Huanye Mo ◽  
Shengli Wu ◽  
Xin Liu ◽  
Kangsheng Tu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Tumor Microenvironment ◽  
External Validation ◽  
Gene Signature ◽  
Metabolic Reprogramming ◽  
Lactate Metabolism ◽  
Related Gene ◽  
High Group ◽  
Cox Regression Analysis

Hepatocellular carcinoma (HCC) is the main subtype of primary liver cancer with high malignancy and poor prognosis. Metabolic reprogramming is a hallmark of cancer and has great importance on the tumor microenvironment (TME). As an abundant metabolite, lactate plays a crucial role in cancer progression and the immunosuppressive TME. Nonetheless, the potential roles of lactate in HCC remain unclear. In this study, we downloaded transcriptomic data of HCC patients with corresponding clinical information from the TCGA and ICGC portals. The TCGA-HCC dataset used as the training cohort, while the ICGC-LIRI-JP dataset was served as an external validation cohort. Cox regression analysis and the LASSO regression model were combined to construct the lactate metabolism-related gene signature (LMRGS). Then, we assessed the clinical significance of LMRGS in HCC. Besides, enriched molecular functions, tumor mutation burden (TMB), infiltrating immune cells, and immune checkpoint were comprehensively analyzed in different LMRGS subgroups. In total, 66 differentially expressed lactate metabolism-related genes (LMRGs) were screened. The functions of LMRGs were mainly enriched in mitochondrial activity and metabolic processes. The LMRGS comprised of six key LMRGs (FKTN, PDSS1, PET117, PUS1, RARS1, and RNASEH1) had significant clinical value for independently predicting the prognosis of HCC patients. The overall survival and median survival of patients in the LMRGS-high group were significantly shorter than in the LMRGS-low group. In addition, there were differences in TMB between the two LMRGS subgroups. The probability of genetic mutations was higher in the LMRGS-high group. Most importantly, the LMRGS reflected the TME characteristics. In the LMRGS-high group, the immune microenvironment presented a suppressed state, accompanied by more inhibitory immune cell infiltration, including follicular helper T cells and regulatory T cells. Additionally, the expression of inhibitory checkpoint molecules was much higher in the LMRGS-high group. Our study suggested that the LMRGS was a robust biomarker to predict the clinical outcomes and evaluate the TME of patients with HCC.

Natural Products Inspired Modulators of Cancer Stem Cells-specific Signaling Pathways Notch and Hedgehog

2019 ◽  
Vol 24 (36) ◽  
pp. 4251-4269 ◽  
Author(s):  
Rocco Palermo ◽  
Francesca Ghirga ◽  
Maria Grazia Piccioni ◽  
Flavia Bernardi ◽  
Nadezda Zhdanovskaya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Anticancer Agents ◽  
Chemical Biology ◽  
Total Syntheses ◽  
Lead Compounds ◽  
Promising Strategy ◽  
Anticancer Drug Discovery

It is nowadays widely accepted that some tumors have a niche of cells endowed with stemness features, which may cause resistance to conventional anticancer therapies and relapse/recurrence of the malignancy. These cells are usually referred to as cancer stem cells (CSCs) and, different from normal cancer cells, are rather quiescent. Targeting CSCs is thus a highly challenging but promising strategy to counteract tumor growth, and to develop innovative anticancer agents. Here, we review the chemical, biological and multidisciplinary efforts that have been spent in targeting CSCsspecific signaling pathways Notch and Hedgehog (Hh) for anticancer drug discovery. In particular, the use of natural products as a valuable source of lead compounds or chemical biology tools is emphasized. Examples of natural products functionalization through semi-synthetic transformations or total syntheses, aimed at improving pharmacokinetics and/or pharmacodynamics properties of natural products in Notch or Hh inhibition, are provided as well.

Tumor microenvironment acid-sensitive liposomes enhanced colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

Nanoscale ◽  
2021 ◽  
Author(s):  
chenglei li ◽  
Zhaohuan Li ◽  
Xue Gong ◽  
Jianhao Liu ◽  
Tingyue Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Crucial Role ◽  
Tumor Invasion ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Promising Strategy

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the “soils” in tumor microenvironment (TME). Accordingly, it would be a promising strategy to...

The C29–C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags

2021 ◽  
Author(s):  
Didik Huswo Utomo ◽  
Akari Fujieda ◽  
Kentaro Tanaka ◽  
Momoko Takahashi ◽  
Kentaro Futaki ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Development ◽  
Anticancer Drug ◽  
Protein Interactions ◽  
Side Chain ◽  
Protein Protein Interactions ◽  
Affinity Tags ◽  
Promising Strategy ◽  
Anticancer Drug Development ◽  
Aplyronine A

Anticancer drug development inspired by natural products based on protein–protein interactions (PPI) is a promising strategy. We developed structurally-simplified C29–C34 side-chain analogs of aplyronine A (ApA), an antitumor marine macrolide....

Nanoengineering of newly designed chlorin e6 derivative for amplified photodynamic therapy via regulating lactate metabolism

Nanoscale ◽  
2021 ◽  
Author(s):  
Xiaohan Qin ◽  
Mengzhu Zhang ◽  
Xu Hu ◽  
Qian Du ◽  
Zhipeng Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Therapeutic Efficacy ◽  
Chlorin E6 ◽  
Lactate Metabolism

Chlorin e6 (Ce6) is a widely utilized photosensitizer in photodynamic therapy (PDT) against tumor growth, but its hydrophobic feature and the hypoxia in tumor microenvironment greatly compromise its therapeutic efficacy....

scholarly journals Validating Antimetastatic Effects of Natural Products in an Engineered Microfluidic Platform Mimicking Tumor Microenvironment

2014 ◽  
Vol 11 (7) ◽  
pp. 2022-2029 ◽  
Author(s):  
Yiming Niu ◽  
Jing Bai ◽  
Roger D. Kamm ◽  
Yitao Wang ◽  
Chunming Wang
Keyword(s):  
Natural Products ◽  
Tumor Microenvironment ◽  
Microfluidic Platform
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