scholarly journals The Macrophages-Microbiota Interplay in Colorectal Cancer (CRC)-Related Inflammation: Prognostic and Therapeutic Significance

2020 ◽  
Vol 21 (18) ◽  
pp. 6866
Author(s):  
Silvia Mola ◽  
Chiara Pandolfo ◽  
Antonio Sica ◽  
Chiara Porta
Keyword(s):  
Colorectal Cancer ◽  
Tumor Development ◽  
Prognostic Indicators ◽  
Functional Heterogeneity ◽  
Therapeutic Approaches ◽  
Effector Cells ◽  
New Therapeutic Approaches ◽  
Cancer Types ◽  
Macrophage Subtypes ◽  
Main Population

Tumor-associated macrophages (TAMs) are the main population of myeloid cells infiltrating solid tumors and the pivotal orchestrators of cancer-promoting inflammation. However, due to their exceptional plasticity, macrophages can be also key effector cells and powerful activators of adaptive anti-tumor immunity. This functional heterogeneity is emerging in human tumors, colorectal cancer (CRC) in particular, where the dynamic co-existence of different macrophage subtypes influences tumor development, outcome, and response to therapies. Intestinal macrophages are in close interaction with enteric microbiota, which contributes to carcinogenesis and affects treatment outcomes. This interplay may be particularly relevant in CRC, one of the most prevalent and lethal cancer types in the world. Therefore, both macrophages and intestinal microbiota are considered promising prognostic indicators and valuable targets for new therapeutic approaches. Here, we discuss the current understanding of the molecular circuits underlying the interplay between macrophages and microbiota in CRC development, progression, and response to both conventional therapies and immunotherapies.

scholarly journals LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 195
Author(s):  
Francisca Dias ◽  
Cristina Almeida ◽  
Ana Luísa Teixeira ◽  
Mariana Morais ◽  
Rui Medeiros
Keyword(s):  
Colorectal Cancer ◽  
Amino Acid ◽  
Cancer Progression ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Amino Acid Transporters ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Colorectal Cancer Progression ◽  
Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

scholarly journals MicroRNA-146a limits tumorigenic inflammation in colorectal cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucien P. Garo ◽  
Amrendra K. Ajay ◽  
Mai Fujiwara ◽  
Galina Gabriely ◽  
Radhika Raheja ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Development ◽  
Myeloid Cell ◽  
Negative Regulator ◽  
Sporadic Colorectal Cancer ◽  
Intestinal Epithelial ◽  
Therapeutic Approaches ◽  
Colonic Inflammation ◽  
Small Molecule Inhibition ◽  
Deficient Mice

AbstractChronic inflammation can drive tumor development. Here, we have identified microRNA-146a (miR-146a) as a major negative regulator of colonic inflammation and associated tumorigenesis by modulating IL-17 responses. MiR-146a-deficient mice are susceptible to both colitis-associated and sporadic colorectal cancer (CRC), presenting with enhanced tumorigenic IL-17 signaling. Within myeloid cells, miR-146a targets RIPK2, a NOD2 signaling intermediate, to limit myeloid cell-derived IL-17-inducing cytokines and restrict colonic IL-17. Accordingly, myeloid-specific miR-146a deletion promotes CRC. Moreover, within intestinal epithelial cells (IECs), miR-146a targets TRAF6, an IL-17R signaling intermediate, to restrict IEC responsiveness to IL-17. MiR-146a within IECs further suppresses CRC by targeting PTGES2, a PGE2 synthesis enzyme. IEC-specific miR-146a deletion therefore promotes CRC. Importantly, preclinical administration of miR-146a mimic, or small molecule inhibition of the miR-146a targets, TRAF6 and RIPK2, ameliorates colonic inflammation and CRC. MiR-146a overexpression or miR-146a target inhibition represent therapeutic approaches that limit pathways converging on tumorigenic IL-17 signaling in CRC.

scholarly journals Porphyrin/Chlorin Derivatives as Promising Molecules for Therapy of Colorectal Cancer

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7268
Author(s):  
Fatima Dandash ◽  
David Y. Leger ◽  
Mona Diab-Assaf ◽  
Vincent Sol ◽  
Bertrand Liagre
Keyword(s):  
Colorectal Cancer ◽  
Photodynamic Therapy ◽  
Side Effects ◽  
Cancer Cells ◽  
The Other ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Porphyrin Derivatives ◽  
Chemotherapeutic Activity ◽  
Anticancer Treatment

Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and their special affinity to cancer cells makes them the ligands par excellence for anticancer drugs. Porphyrin derivatives are used as the most important photosensitizers (PSs) for photodynamic therapy (PDT), which is a promising approach for anticancer treatment. Nevertheless, the lack of solubility and selectivity of the large majority of these macrocycles led to the development of different photosensitizer complexes. In addition, targeting agents or nanoparticles were used to increase the efficiency of these macrocycles for PDT applications. On the other hand, gold tetrapyrrolic macrocycles alone showed very interesting chemotherapeutic activity without PDT. In this review, we discuss the most important porphyrin derivatives, alone or associated with other drugs, which have been found effective against CRC, as we describe their modifications and developments through substitutions and delivery systems.

scholarly journals Role of Extracellular Matrix in Gastrointestinal Cancer-Associated Angiogenesis

2020 ◽  
Vol 21 (10) ◽  
pp. 3686 ◽  
Author(s):  
Eva Andreuzzi ◽  
Alessandra Capuano ◽  
Evelina Poletto ◽  
Eliana Pivetta ◽  
Albina Fejza ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Cell Function ◽  
Current Knowledge ◽  
Tumor Development ◽  
Therapy Response ◽  
Therapeutic Approaches ◽  
Endothelial Cell Function ◽  
New Therapeutic Approaches

Gastrointestinal tumors are responsible for more cancer-related fatalities than any other type of tumors, and colorectal and gastric malignancies account for a large part of these diseases. Thus, there is an urgent need to develop new therapeutic approaches to improve the patients’ outcome and the tumor microenvironment is a promising arena for the development of such treatments. In fact, the nature of the microenvironment in the different gastrointestinal tracts may significantly influence not only tumor development but also the therapy response. In particular, an important microenvironmental component and a potential therapeutic target is the vasculature. In this context, the extracellular matrix is a key component exerting an active effect in all the hallmarks of cancer, including angiogenesis. Here, we summarized the current knowledge on the role of extracellular matrix in affecting endothelial cell function and intratumoral vascularization in the context of colorectal and gastric cancer. The extracellular matrix acts both directly on endothelial cells and indirectly through its remodeling and the consequent release of growth factors. We envision that a deeper understanding of the role of extracellular matrix and of its remodeling during cancer progression is of chief importance for the development of new, more efficacious, targeted therapies.

scholarly journals The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Ranjbar ◽  
Rasoul Salehi ◽  
Shaghayegh Haghjooy Javanmard ◽  
Laleh Rafiee ◽  
Habibollah Faraji ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Genetic Factors ◽  
Fusobacterium Nucleatum ◽  
Published Data ◽  
Structural Components ◽  
Epigenetic Factors ◽  
Therapeutic Approaches ◽  
Mortality And Morbidity ◽  
New Therapeutic Approaches

AbstractColorectal cancer (CRC) is the third most common cause of cancer globally and the fourth attributable cause of mortality and morbidity due to cancer. An emerging factor contributing to CRC is the gut microbiota and the cellular changes associated with it. Further insights on this may help in the prevention, diagnosis and new therapeutic approaches to colorectal cancer. In most cases of CRC, genetic factors appear to contribute less to its aetiology than environmental and epigenetic factors; therefore, it may be important to investigate these environmental factors, their effects, and the mechanisms that may contribute to this cancer. The gut microbiota has recently been highlighted as a potential risk factor that may affect the structural components of the tumor microenvironment, as well as free radical and enzymatic metabolites directly, or indirectly. Many studies have reported changes in the gut microbiota of patients with colorectal cancer. What is controversial is whether the cancer is the cause or consequence of the change in the microbiota. There is strong evidence supporting both possibilities. The presence of Fusobacterium nucleatum in human colorectal specimens has been demonstrated by RNA-sequencing. F. nucleatum has been shown to express high levels of virulence factors such as FadA, Fap2 and MORN2 proteins. Our review of the published data suggest that F. nucleatum may be a prognostic biomarker of CRC risk, and hence raises the potential of antibiotic treatment of F. nucleatum for the prevention of CRC.

scholarly journals Insights from IgE Immune Surveillance in Allergy and Cancer for Anti-Tumour IgE Treatments

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4460
Author(s):  
Alex J. McCraw ◽  
Jitesh Chauhan ◽  
Heather J. Bax ◽  
Chara Stavraka ◽  
Gabriel Osborn ◽  
...  
Keyword(s):  
Functional Data ◽  
Immune Surveillance ◽  
Epidemiological Data ◽  
Therapeutic Approaches ◽  
Complex Interplay ◽  
Effector Cells ◽  
Patient Groups ◽  
Cancer Types ◽  
Antibody Class ◽  
High Risk Cancer

IgE, the predominant antibody class of the allergic response, is known for its roles in protecting against parasites; however, a growing body of evidence indicates a significant role for IgE and its associated effector cells in tumour immunosurveillance, highlighted by the field of AllergoOncology and the successes of the first-in-class IgE cancer therapeutic MOv18. Supporting this concept, substantial epidemiological data ascribe potential roles for IgE, allergy, and atopy in protecting against specific tumour types, with a corresponding increased cancer risk associated with IgE immunodeficiency. Here, we consider how epidemiological data in combination with functional data reveals a complex interplay of IgE and allergy with cancer, which cannot be explained solely by one of the existing conventional hypotheses. We furthermore discuss how, in turn, such data may be used to inform future therapeutic approaches, including the clinical management of different patient groups. With epidemiological findings highlighting several high-risk cancer types protected against by high IgE levels, it is possible that use of IgE-based therapeutics for a range of malignant indications may offer efficacy to complement that of established IgG-class antibodies.

scholarly journals A summary of current NKG2D-based CAR clinical trials

2021 ◽  
Author(s):  
Sophie Curio ◽  
Gustav Jonsson ◽  
Sonja Marinovic ◽  
Keyword(s):  
Clinical Trials ◽  
Tumor Cells ◽  
Treatment Options ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
New Therapeutic Approaches ◽  
Important Player ◽  
Cancer Types ◽  
Stressed Cells ◽  
Cancer Immunotherapies

Abstract Cancer immunotherapies have significantly improved patient survival and treatment options in recent years. Nonetheless, the success of immunotherapy is limited to certain cancer types and specific subgroups of patients, making the development of new therapeutic approaches a topic of ongoing research. Chimeric antigen receptor (CAR) cells are engineered immune cells that are programmed to specifically eliminate cancer cells. Ideally, a CAR recognizes antigens that are restricted to tumor cells to avoid off-target effects. NKG2D is an activating immunoreceptor and an important player in anti-tumor immunity due to its ability to recognize tumor cells and initiate an anti-tumor immune response. Ligands for NKG2D are expressed on malignant or stressed cells and typically absent from healthy tissue, making it a promising CAR candidate. Here, we provide a summary of past and ongoing NKG2D-based CAR clinical trials and comment on potential pitfalls.

scholarly journals Efficacy of a Three Drug-Based Therapy for Neuroblastoma in Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6753
Author(s):  
Patrizia Garbati ◽  
Raffaella Barbieri ◽  
Matilde Calderoni ◽  
Francesca Baldini ◽  
Mario Nizzari ◽  
...  
Keyword(s):  
Early Childhood ◽  
Multidrug Resistance ◽  
High Risk ◽  
Therapeutic Approaches ◽  
Pharmacological Approach ◽  
New Therapeutic Approaches ◽  
Cancer Types ◽  
Approved Drugs ◽  
Chemotherapy Efficacy ◽  
Fda Approved Drugs

High-risk neuroblastoma (HR-NB) still remains the most dangerous tumor in early childhood. For this reason, the identification of new therapeutic approaches is of fundamental importance. Recently, we combined the conventional pharmacological approach to NB, represented by cisplatin, with fendiline hydrochloride, an inhibitor of several transporters involved in multidrug resistance of cancer cells, which demonstrated an enhancement of the ability of cisplatin to induce apoptosis. In this work, we co-administrated acetazolamide, a carbonic anhydrase isoform IX (CAIX) inhibitor which was reported to increase chemotherapy efficacy in various cancer types, to the cisplatin/fendiline approach in SKNBE2 xenografts in NOD-SCID mice with the aim of identifying a novel and more effective treatment. We observed that the combination of the three drugs increases more than twelvefold the differences in the cytotoxic activity of cisplatin alone, leading to a remarkable decrease of the expression of malignancy markers. Our conclusion is that this approach, based on three FDA-approved drugs, may constitute an appropriate improvement of the pharmacological approach to HR-NB.

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