scholarly journals Targeting Tumor Microenvironment for Cancer Therapy

2019 ◽  
Vol 20 (4) ◽  
pp. 840 ◽  
Author(s):  
Catarina Roma-Rodrigues ◽  
Rita Mendes ◽  
Pedro Baptista ◽  
Alexandra Fernandes
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Tissue ◽  
Physiological State ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
Cancer Therapies ◽  
Multicellular Tumor Spheroids ◽  
Common Features ◽  
Anti Cancer

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response from neighbor stromal cells (e.g., fibroblasts) and immune cells (lymphocytes and macrophages), inducing angiogenesis and, ultimately, resulting in metastasis. Exosomes secreted by TME cells are central players in all these events. The TME profile is preponderant on prognosis and impacts efficacy of anti-cancer therapies. Hence, a big effort has been made to develop new therapeutic strategies towards a more efficient targeting of TME. These efforts focus on: (i) therapeutic strategies targeting TME components, extending from conventional therapeutics, to combined therapies and nanomedicines; and (ii) the development of models that accurately resemble the TME for bench investigations, including tumor-tissue explants, “tumor on a chip” or multicellular tumor-spheroids.

scholarly journals How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Alessandra Ferraresi ◽  
Carlo Girone ◽  
Andrea Esposito ◽  
Chiara Vidoni ◽  
Letizia Vallino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Cell Metabolism ◽  
Metabolic Stress ◽  
Metastatic Potential ◽  
Cancer Therapies ◽  
Anti Cancer

Ovarian cancer (OC) is characterized by a high mortality rate due to the late diagnosis and the elevated metastatic potential. Autophagy, a lysosomal-driven catabolic process, contributes to the macromolecular turnover, cell homeostasis, and survival, and as such, it represents a pathway targetable for anti-cancer therapies. It is now recognized that the vascularization and the cellular composition of the tumor microenvironment influence the development and progression of OC by controlling the availability of nutrients, oxygen, growth factors, and inflammatory and immune-regulatory soluble factors that ultimately impinge on autophagy regulation in cancer cells. An increasing body of evidence indicates that OC carcinogenesis is associated, at least in the early stages, to insufficient autophagy. On the other hand, when the tumor is already established, autophagy activation provides a survival advantage to the cancer cells that face metabolic stress and protects from the macromolecules and organelles damages induced by chemo- and radiotherapy. Additionally, upregulation of autophagy may lead cancer cells to a non-proliferative dormant state that protects the cells from toxic injuries while preserving their stem-like properties. Further to complicate the picture, autophagy is deregulated also in stromal cells. Thus, changes in the tumor microenvironment reflect on the metabolic crosstalk between cancer and stromal cells impacting on their autophagy levels and, consequently, on cancer progression. Here, we present a brief overview of the role of autophagy in OC hallmarks, including tumor dormancy, chemoresistance, metastasis, and cell metabolism, with an emphasis on the bidirectional metabolic crosstalk between cancer cells and stromal cells in shaping the OC microenvironment.

scholarly journals Purinergic P2X7 Receptor: A Cation Channel Sensitive to Tumor Microenvironment

2019 ◽  
Vol 14 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Giorgia Scarpellino ◽  
Tullio Genova ◽  
Luca Munaron
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
P2x7 Receptor ◽  
Purinergic Receptor ◽  
Purinergic Signalling ◽  
Cancer Therapies ◽  
Cell Functions ◽  
Anti Cancer ◽  
Purinergic P2x7 Receptor ◽  
And Function

Background: Purinergic signalling is involved in several physiological and pathophysiological processes. P2X7 Receptor (P2X7R) is a calcium-permeable ion channel that is gaining interest as a potential therapeutic target for the treatment of different diseases including inflammation, pain, psychiatric disorders and cancer. P2X7R is ubiquitously expressed and sensitive to high ATP levels, usually found in tumor microenvironment. P2X7R regulates several cell functions, from migration to cell death, but its selective contribution to tumor progression remains controversial.Objective:Current review was conducted to check involvement of P2X7R use in cancer treatment.Methods:We review the most recent patents focused on the use of P2X7R in the treatment of cancer.Results:P2X7R is an intriguing purinergic receptor that plays different roles in tumor progression.Conclusion:Powerful strategies able to selectively interfere with its expression and function should reveal helpful in the development of new anti-cancer therapies.

scholarly journals Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

2021 ◽  
Vol 10 ◽  
Author(s):  
Aukie Hooglugt ◽  
Miesje M. van der Stoel ◽  
Reinier A. Boon ◽  
Stephan Huveneers
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Lymphatic Vessels ◽  
Cancer Therapies ◽  
Tumor Cell Growth ◽  
Vascular Normalization ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Tumor Endothelium

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.

scholarly journals Chronic Stress: Impacts on Tumor Microenvironment and Implications for Anti-Cancer Treatments

2021 ◽  
Vol 9 ◽  
Author(s):  
Wentao Tian ◽  
Yi Liu ◽  
Chenghui Cao ◽  
Yue Zeng ◽  
Yue Pan ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Chronic Stress ◽  
Epithelial Mesenchymal Transition ◽  
Multi Drug Resistance ◽  
Cancer Therapies ◽  
Negative Effects ◽  
Cancer Treatments ◽  
Mesenchymal Transition ◽  
Anti Cancer

Chronic stress is common among cancer patients due to the psychological, operative, or pharmaceutical stressors at the time of diagnosis or during the treatment of cancers. The continuous activations of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as results of chronic stress, have been demonstrated to take part in several cancer-promoting processes, such as tumorigenesis, progression, metastasis, and multi-drug resistance, by altering the tumor microenvironment (TME). Stressed TME is generally characterized by the increased proportion of cancer-promoting cells and cytokines, the reduction and malfunction of immune-supportive cells and cytokines, augmented angiogenesis, enhanced epithelial-mesenchymal transition, and damaged extracellular matrix. For the negative effects that these alterations can cause in terms of the efficacies of anti-cancer treatments and prognosis of patients, supplementary pharmacological or psychotherapeutic strategies targeting HPA, SNS, or psychological stress may be effective in improving the prognosis of cancer patients. Here, we review the characteristics and mechanisms of TME alterations under chronic stress, their influences on anti-cancer therapies, and accessory interventions and therapies for stressed cancer patients.

scholarly journals Decoding the Roles of Astrocytes and Hedgehog Signaling in Medulloblastoma

2021 ◽  
Vol 28 (4) ◽  
pp. 3058-3070
Author(s):  
Terence Teixeira Duarte ◽  
Silvia Aparecida Teixeira ◽  
Luis Gonzalez-Reyes ◽  
Rui Manuel Reis
Keyword(s):  
Tumor Microenvironment ◽  
Sonic Hedgehog ◽  
Stromal Cells ◽  
Hedgehog Signaling ◽  
Prognostic Markers ◽  
Therapeutic Strategies ◽  
Molecular Networks ◽  
Transduction Mechanisms ◽  
Tumoral Cells ◽  
Multiple Interactions

The molecular evolution of medulloblastoma is more complex than previously imagined, as emerging evidence suggests that multiple interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting sonic hedgehog (SHH) subgroup medulloblastoma (MB) and provide an overview of MB progression through SHH expression and signal transduction mechanisms into the complex tumor microenvironment. In addition, we highlight the associations between tumor and stromal cells as possible prognostic markers that could be targeted with new therapeutic strategies.

scholarly journals Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2057 ◽  
Author(s):  
Shweta Joshi
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Genetic Alterations ◽  
Future Directions ◽  
Pediatric Tumor ◽  
Normal Tissues ◽  
Recent Advances ◽  
Future Potential

Neuroblastoma (NB) is the most common pediatric tumor malignancy that originates from the neural crest and accounts for more than 15% of all the childhood deaths from cancer. The neuroblastoma cancer research has long been focused on the role of MYCN oncogene amplification and the contribution of other genetic alterations in the progression of this malignancy. However, it is now widely accepted that, not only tumor cells, but the components of tumor microenvironment (TME), including extracellular matrix, stromal cells and immune cells, also contribute to tumor progression in neuroblastoma. The complexity of different components of tumor stroma and their resemblance with surrounding normal tissues pose huge challenges for therapies targeting tumor microenvironment in NB. Hence, the detailed understanding of the composition of the TME of NB is crucial to improve existing and future potential immunotherapeutic approaches against this childhood cancer. In this review article, I will discuss different components of the TME of NB and the recent advances in the strategies, which are used to target the tumor microenvironment in neuroblastoma.

scholarly journals The Influence of Tumor Microenvironment on Immune Escape of Melanoma

2020 ◽  
Vol 21 (21) ◽  
pp. 8359 ◽  
Author(s):  
Aleksandra Simiczyjew ◽  
Ewelina Dratkiewicz ◽  
Justyna Mazurkiewicz ◽  
Marcin Ziętek ◽  
Rafał Matkowski ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Cell Types ◽  
Melanoma Cells ◽  
Cancer Therapies ◽  
System A ◽  
Anti Cancer ◽  
Low Efficiency ◽  
Inflammatory Molecules

The low efficiency of currently-used anti-cancer therapies poses a serious challenge, especially in the case of malignant melanoma, a cancer characterized by elevated invasiveness and relatively high mortality rate. The role of the tumor microenvironment in the progression of melanoma and its acquisition of resistance to treatment seems to be the main focus of recent studies. One of the factors that, in normal conditions, aids the organism in its fight against the cancer and, following the malignant transformation, adapts to facilitate the development of the tumor is the immune system. A variety of cell types, i.e., T and B lymphocytes, macrophages, and dendritic and natural killer cells, as well as neutrophils, support the growth and invasiveness of melanoma cells, utilizing a plethora of mechanisms, including secretion of pro-inflammatory molecules, induction of inhibitory receptors expression, or depletion of essential nutrients. This review provides a comprehensive summary of the processes regulated by tumor-associated cells that promote the immune escape of melanoma cells. The described mechanisms offer potential new targets for anti-cancer treatment and should be further studied to improve currently-employed therapies.

scholarly journals Emerging data supporting stromal cell therapeutic potential in cancer: reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

2020 ◽  
Vol 17 (4) ◽  
pp. 828-841
Author(s):  
Armel H. Nwabo Kamdje ◽  
Paul F. Seke Etet ◽  
Richard Tagne Simo ◽  
Lorella Vecchio ◽  
Kiven Erique Lukong ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Therapeutic Potential ◽  
Anti Cancer

scholarly journals Improving Cancer Immunotherapy by Targeting the Hypoxic Tumor Microenvironment: New Opportunities and Challenges

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1083 ◽  
Author(s):  
Muhammad Zaeem Noman ◽  
Meriem Hasmim ◽  
Audrey Lequeux ◽  
Malina Xiao ◽  
Caroline Duhem ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Molecular Mechanisms ◽  
Cancer Therapies ◽  
Hallmarks Of Cancer ◽  
The Past ◽  
Therapeutic Value ◽  
Anti Cancer ◽  
Microenvironmental Factors ◽  
Hypoxic Tumor ◽  
Insight Into

Initially believed to be a disease of deregulated cellular and genetic expression, cancer is now also considered a disease of the tumor microenvironment. Over the past two decades, significant and rapid progress has been made to understand the complexity of the tumor microenvironment and its contribution to shaping the response to various anti-cancer therapies, including immunotherapy. Nevertheless, it has become clear that the tumor microenvironment is one of the main hallmarks of cancer. Therefore, a major challenge is to identify key druggable factors and pathways in the tumor microenvironment that can be manipulated to improve the efficacy of current cancer therapies. Among the different tumor microenvironmental factors, this review will focus on hypoxia as a key process that evolved in the tumor microenvironment. We will briefly describe our current understanding of the molecular mechanisms by which hypoxia negatively affects tumor immunity and shapes the anti-tumor immune response. We believe that such understanding will provide insight into the therapeutic value of targeting hypoxia and assist in the design of innovative combination approaches to improve the efficacy of current cancer therapies, including immunotherapy.

scholarly journals How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2550
Author(s):  
Roberto Zefferino ◽  
Claudia Piccoli ◽  
Sante Di Gioia ◽  
Nazzareno Capitanio ◽  
Massimo Conese
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Therapeutic Strategies ◽  
Invasion And Metastasis ◽  
Complex Interplay ◽  
Cancer Disease ◽  
Novel Therapeutic Strategies ◽  
Early Late ◽  
Novel Therapeutic

Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.

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