Co-Delivery of IL-12 Cytokine Gene and Cisplatin Prodrug by Polymetformin-Conjugated Nanosystem for Chemo-Gene Cancer Treatment Through Chemotherapy Sensitization and Tumor Microenvironment Modulation

2021 ◽  
Author(s):  
Yue Sun ◽  
Tong Yang ◽  
Yifan Li ◽  
Jiayu Yang ◽  
Rongyue Zhu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cytokine Gene

Matrix Metalloproteinases (MMPs) in Targeted Drug Delivery: Synthesis of a Potent and Highly Selective Inhibitor against Matrix Metalloproteinase- 7

2020 ◽  
Vol 20 (27) ◽  
pp. 2459-2471
Author(s):  
Ling-Li Wang ◽  
Bing Zhang ◽  
Ming-Hua Zheng ◽  
Yu-Zhong Xie ◽  
Chang-Jiang Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Matrix Metalloproteinases ◽  
Cancer Treatment ◽  
Targeted Drug Delivery ◽  
Selective Inhibitor ◽  
Migration And Invasion ◽  
Side Chains ◽  
Mesenchymal Transition ◽  
Targeted Drug

Background: Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. MMPs have reportedly shown great potentials in the degradation of the Extracellular Matrix (ECM), have shown great potentials in targeting bioactive and imaging agents in cancer treatment. MMPs could provoke Epithelial to Mesenchymal Transition (EMT) of cancer cells and manipulate their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Therefore, targeting and particularly inhibiting MMPs within the tumor microenvironment is an effective strategy for cancer treatment. Based on this idea, different MMP inhibitors (MMPIs) have been developed to manipulate the tumor microenvironment towards conditions appropriate for the actions of antitumor agents. Studies are ongoing to improve the selectivity and specificity of MMPIs. Structural optimization has facilitated the discovery of selective inhibitors of the MMPs. However, so far no selective inhibitor for MMP-7 has been proposed. Aims: This study aims to comprehensively review the potentials and advances in applications of MMPs particularly MMP-7 in targeted cancer treatment approaches with the main focus on targeted drug delivery. Different targeting strategies for manipulating and inhibiting MMPs for the treatment of cancer are discussed. MMPs are upregulated at all stages of expression in cancers. Different MMP subtypes have shown significant targeting applicability at the genetic, protein, and activity levels in both physiological and pathophysiological conditions in a variety of cancers. The expression of MMPs significantly increases at advanced cancer stages, which can be used for controlled release in cancers in advance stages. Methods: Moreover, this study presents the synthesis and characteristics of a new and highly selective inhibitor against MMP-7 and discusses its applications in targeted drug delivery systems for therapeutics and diagnostics modalities. Results: Our findings showed that the structure of the inhibitor P3’ side chains play the crucial role in developing an optimized MMP-7 inhibitor with high selectivity and significant degradation activities against ECM. Conclusion: Optimized NDC can serve as a highly potent and selective inhibitor against MMP-7 following screening and optimization of the P3’ side chains, with a Ki of 38.6 nM and an inhibitory selectivity of 575 of MMP-7 over MMP-1.

Treatment of solid tumors using bispecific anti-PDL-1/ICOS antibody

2021 ◽  
Author(s):  
Martin Perez-Santos ◽  
Maricruz Anaya-Ruiz ◽  
Gabriela Sanchez-Esgua ◽  
Luis Villafaña-Diaz ◽  
Diana Barron-Villaverde
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Potential Application ◽  
Poor Prognosis ◽  
Bispecific Antibody ◽  
Control Points ◽  
Immune Control ◽  
Ct26 Model

PD-L1 and ICOS are immune control points in cancer and their presence in cancer tends to have a poor prognosis. WO2019122882 patent describes a bispecific antibody that targets PDL-1/ICOS with the potential application of cancer treatment. WO2019122882 patent describes a bispecific antibody with antitumor efficacy in CT26 model through of the depletion of TReg cells and improved ratio of CD8+ T cells: TReg in tumor microenvironment. The anti-PDL-1/ICOS antibody is new; however, only preclinical assays are shown using colon carcinoma model. So far, there are no reports of clinical trials to evaluate the safety, toxicity and efficacy, but it will be of great interest to analyze in the future if this antibody surpasses the action of the combinatorial therapy in cancer.

Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy

2018 ◽  
Vol 474 (4) ◽  
pp. 407-420 ◽  
Author(s):  
Alessandra Tuccitto ◽  
Eriomina Shahaj ◽  
Elisabetta Vergani ◽  
Simona Ferro ◽  
Veronica Huber ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Treatment Efficacy

scholarly journals pH-responded Hollow Fe–Gallic Acid Coordination Polymer for Multimodal Synergistic-therapy and MRI of Cancer

2021 ◽  
Author(s):  
Congcong Liu ◽  
Chengcheng Li ◽  
Sen Jiang ◽  
Cheng Zhang ◽  
Yang Tian
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Coordination Polymer ◽  
Cancer Treatment ◽  
Gallic Acid ◽  
Drug Carriers ◽  
Clinical Cancer

Tumor-microenvironment (TME) responding nanostructures are attractive for drug delivery in clinical cancer treatment. The coordination polymer Fe–Gallic Acid (Fe-GA) is one of the promising drug carriers due to its pH-responding,...

scholarly journals Exosomes in the Tumor Microenvironment: From Biology to Clinical Applications

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2617
Author(s):  
Vitor Rodrigues da Costa ◽  
Rodrigo Pinheiro Araldi ◽  
Hugo Vigerelli ◽  
Fernanda D’Ámelio ◽  
Thais Biude Mendes ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Biology ◽  
Clinical Applications ◽  
Future Prospects ◽  
Hallmarks Of Cancer ◽  
Cancer Heterogeneity ◽  
Important Health ◽  
Clinical Potential

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.

scholarly journals Manipulation of the tumor microenvironment by cytokine gene transfection enhances dendritic cell‐based immunotherapy

2019 ◽  
Vol 2 (1) ◽  
pp. 5-17
Author(s):  
Daluthgamage Patsy Himali Wijesekera ◽  
Eiji Yuba ◽  
Nadeeka Harshini De Silva ◽  
Shun‐ichi Watanabe ◽  
Masaya Tsukamoto ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Tumor Microenvironment ◽  
Gene Transfection ◽  
Cytokine Gene

Application of a robust and novel ex vivo platform mimicking patient heterogenous tumor microenvironment for personalized cancer treatment.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 6029-6029
Author(s):  
Kanaka Govind Babu ◽  
Biswanath Majumder ◽  
Saravanan Thiyagarajan ◽  
Baraneedharan Ulaganathan ◽  
Rajagopal Surindran ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Ex Vivo ◽  
Personalized Cancer

14. Role of tumor microenvironment in cryosurgery: Opportunities for new approaches to multi-modality cancer treatment

Cryobiology ◽  
2013 ◽  
Vol 66 (3) ◽  
pp. 346
Author(s):  
Robert J. Griffin ◽  
Gal Shafirstein ◽  
John Bischof ◽  
Klressa Barnes
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
New Approaches

Role of the Immune Component of Tumor Microenvironment in the Efficiency of Cancer Treatment: Perspectives for the Personalized Therapy

2017 ◽  
Vol 23 (32) ◽  
pp. 4807-4826 ◽  
Author(s):  
Marina Stakheyeva ◽  
Vladimir Riabov ◽  
Irina Mitrofanova ◽  
Nikolai Litviakov ◽  
Evgeny Choynzonov ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Immune Cells ◽  
Critical Factor ◽  
Cancer Diagnostics ◽  
Patient Specific ◽  
Intratumor Heterogeneity ◽  
Therapeutic Approaches

Despite significant progress in cancer diagnostics and development of novel therapeutic regimens, successful treatment of advanced forms of cancer is still a challenge and may require personalized therapeutic approaches. In this review, we analyzed major mechanisms responsible for tumor cells chemoresistance and emphasized that intratumor heterogeneity is a critical factor that limits efficiency of cancer treatment. Intratumor heterogeneity is caused by genomic instability in cancer cells, resulting in the selection of resistant clones. Moreover, cancer cells in solid tumors are surrounded by cellular and molecular microenvironment that actively influences tumor cell behavior. Local tumor microenvironment (TME) consisting of immune cells with diverse phenotypes and functions strongly contributes to intratumor heterogeneity and modulates responses to treatment. Thus, targeting specific components of TME is a novel treatment strategy that can improve the outcome of conventional anti-cancer therapy. Here, we discuss modern immunotherapeutic approaches based on targeting tumorinfiltrating immune cells including neutrophils, dendritic cells, NK cells, T cells, B cells and macrophages. Among those, tumor-associated macrophages (TAM) that display a pronounced heterogeneity and phenotypic plasticity appear to be a major component in the TME of solid tumors, and emerge as perspective targets for cancer immunotherapy. TAM intratumor heterogeneity and the possible existence of patient-specific phenotype signature generate the basis for the development of individualized TAM-based therapeutic approaches.

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