Biochimica et biophysica acta. Reviews on cancer最新文献

Canonically, the transcription factor interferon regulatory factor 5 (IRF5) is a key mediator of innate and adaptive immunity downstream of pathogen recognition receptors such as Toll-like receptors (TLRs). Hence, dysregulation of IRF5 function has been widely implicated in inflammatory and autoimmune diseases. Over the last few decades, dysregulation of IRF5 expression has been also reported in hematologic malignancies and solid cancers that support a role for IRF5 in malignant transformation, tumor immune regulation, clinical prognosis, and treatment response. This review will provide an in-depth overview of the current literature regarding the mechanisms by which IRF5 functions as either a tumor suppressor or oncogene, its role in metastasis, regulation of the tumor-immune microenvironment, utility as a prognostic indicator of disease, and new developments in IRF5 therapeutics that may be used to remodel tumor immunity.

Ovarian cancer is a less common tumor in women compared to cervical or breast cancer, however it is more malignant and has worse outcomes. Ovarian cancer patients still have a five-year survival rate < 50% despite advances in therapy. Due to recent developments in immune checkpoint inhibitors (ICIs), cancer immunotherapy has attracted increased interest. Pyroptosis is a highly inflammatory form of cell death, which is essential for bridging innate and adaptive immunity, and is involved in immune regulation within the tumor microenvironment (TME). Recent research has shown that pyroptosis can promote immunotherapy of ovarian cancer, including treatment with chimeric antigen receptor T-cells (CAR-T) or ICIs. Moreover, inflammasomes, various signaling pathways and lncRNAs can all affect pyroptosis in ovarian cancer. Here we discuss how pyroptosis affects the development and progression of ovarian cancer as well as the TME. We also provide a summary of small molecule drugs that could target pyroptotic cell death processes and may be useful in ovarian cancer therapy.

Glioblastoma multiforme is a highly malignant brain tumor with significant intra- and intertumoral heterogeneity known for its aggressive nature and poor prognosis. The complex signaling cascade that regulates this heterogeneity makes targeted drug therapy ineffective. The development of an optimal preclinical model is crucial for the comprehension of molecular heterogeneity and enhancing therapeutic efficacy. The ideal model should establish a relationship between various oncogenes and their corresponding responses. This review presents an analysis of preclinical in vivo and in vitro models that have contributed to the advancement of knowledge in model development. The experimental designs utilized in vivo models consisting of both immunodeficient and immunocompetent mice induced with intracranial glioma. The transgenic model was generated using various techniques, like the viral vector delivery system, transposon system, Cre-LoxP model, and CRISPR-Cas9 approaches. The utilization of the patient-derived xenograft model in glioma research is valuable because it closely replicates the human glioma microenvironment, providing evidence of tumor heterogeneity. The utilization of in vitro techniques in the initial stages of research facilitated the comprehension of molecular interactions. However, these techniques are inadequate in reproducing the interactions between cells and extracellular matrix (ECM). As a result, bioengineered 3D-in vitro models, including spheroids, scaffolds, and brain organoids, were developed to cultivate glioma cells in a three-dimensional environment. These models have enabled researchers to understand the influence of ECM on the invasive nature of tumors. Collectively, these preclinical models effectively depict the molecular pathways and facilitate the evaluation of multiple molecules while tailoring drug therapy.

Despite extensive research and refined therapeutic options, the survival for metastasized uveal melanoma (UM) patients has not improved significantly. UM, a malignant tumor originating from melanocytes in the uveal tract, can be asymptomatic and small tumors may be detected only during routine ophthalmic exams; making early detection and treatment difficult. UM is the result of a number of characteristic somatic alterations which are associated with prognosis. Although UM morphology and biology have been extensively studied, there are significant gaps in our understanding of the early stages of UM tumor evolution and effective treatment to prevent metastatic disease remain elusive. A better understanding of the mechanisms that enable UM cells to thrive and successfully metastasize is crucial to improve treatment efficacy and survival rates. For more than forty years, animal models have been used to investigate the biology of UM. This has led to a number of essential mechanisms and pathways involved in UM aetiology. These models have also been used to evaluate the effectiveness of various drugs and treatment protocols. Here, we provide an overview of the molecular mechanisms and pharmacological studies using mouse and zebrafish UM models. Finally, we highlight promising therapeutics and discuss future considerations using UM models such as optimal inoculation sites, use of BAP1^mut-cell lines and the rise of zebrafish models.

Despite the extensive efforts to find effective therapeutic strategies, glioblastoma (GBM) remains a therapeutic challenge with dismal prognosis of survival. Over the last decade the role of stress responses in GBM therapy has gained a great deal of attention, since depending on the duration and intensity of these cellular programs they can be cytoprotective or promote cancer cell death. As such, initiation of the UPR, autophagy or oxidative stress may either impede or facilitate drug-mediated cell killing. In this review, we summarize the mechanisms that regulate ER stress, autophagy, and oxidative stress during GBM development and progression to later discuss the involvement of these stress pathways in the response to different treatments. We also discuss how a precise understanding of the molecular mechanisms regulating stress responses evoked by different pharmacological agents could decisively contribute to the design of novel and more effective combinational treatments against brain malignancies.

This review delves into the most recent research on the metabolic adaptability of cancer cells and examines how their metabolic functions can impact their progression into metastatic forms. We emphasize the growing significance of lipid metabolism and dietary lipids within the tumor microenvironment, underscoring their influence on tumor progression. Additionally, we present an outline of the interplay between metabolic processes and the epigenome of cancer cells, underscoring the importance regarding the metastatic process. Lastly, we examine the potential of targeting metabolism as a therapeutic approach in combating cancer progression, shedding light on innovative drugs/targets currently undergoing preclinical evaluation.

Cancer patients are often diagnosed with venous thromboembolism (VTE), a cardiovascular disease that substantially decreases their quality of life and survival rate. Haemostasis in these patients is deregulated, which is reflected in the common presentation of a blood hypercoagulation state. Despite the inconsistent results, existing evidence suggests that the expression of microRNAs (miRNAs) is deregulated in the context of venous thrombogenesis in the general population. However, few miRNAs are known to be linked to cancer-associated VTE due to the lack of studies with oncological patients. Parallelly, coagulation factor III, also known as tissue factor (TF), tissue factor pathway inhibitor 1 (TFPI1) and tissue factor pathway inhibitor 2 (TFPI2) have been proposed to have a central role in cancer-associated VTE and tumour progression. Yet, contrary to what was expected, the role of miRNAs targeting the TF coagulation pathway (or extrinsic coagulation pathway) is poorly explored in cancer-induced thrombogenesis. In this review, in addition to miRNAs implicated in VTE, TF and TFPI1/2-targeting miRNAs were revised. Future studies should clarify the implications of these non-coding RNAs in tumour coagulome.

High-grade serous ovarian cancer (HGSOC) is the most frequent and aggressive type of epithelial ovarian cancer, with high recurrence rate and chemoresistance being the main issues in its clinical management. HGSOC is specifically challenging due to the metastatic dissemination via spheroids in the ascitic fluid. The HGSOC spheroids represent the invasive and chemoresistant cellular fraction, which is impossible to investigate in conventional two-dimensional (2D) monolayer cell cultures lacking critical cell-to-cell and cell-extracellular matrix interactions. Three-dimensional (3D) HGSOC cultures, where cells aggregate and exhibit relevant interactions, offer a promising in vitro model of peritoneal metastasis and multicellular drug resistance. This review summarizes recent studies of HGSOC in 3D culture conditions and highlights the role of multicellular HGSOC spheroids and ascitic environment in HGSOC metastasis and chemoresistance.

Cancer metastasis is a complex process influenced by various factors, including epithelial-mesenchymal transition (EMT), tumor cell proliferation, tumor microenvironment, and cellular metabolic status, which remains a significant challenge in clinical oncology, accounting for a majority of cancer-related deaths. TEAD4, a key mediator of the Hippo signaling pathway, has been implicated in regulating these factors that are all critical in the metastatic cascade. TEAD4 drives tumor metastasis and chemoresistance, and its upregulation is associated with poor prognosis in many types of cancers, making it an attractive target for therapeutic intervention. TEAD4 promotes EMT by interacting with coactivators and activating the transcription of genes involved in mesenchymal cell characteristics and extracellular matrix remodeling. Additionally, TEAD4 enhances the stemness of cancer stem cells (CSCs) by regulating the expression of genes associated with CSC maintenance. TEAD4 contributes to metastasis by modulating the secretion of paracrine factors and promoting heterotypic cellular communication. In this paper, we highlight the central role of TEAD4 in cancer metastasis and chemoresistance and its impact on various aspects of tumor biology. Understanding the mechanistic basis of TEAD4-mediated processes can facilitate the development of targeted therapies and combination approaches to combat cancer metastasis and improve treatment outcomes.

Nitric oxide (NO) generated from nitric oxide synthase (NOS) exerts a dichotomous effect in melanoma, suppressing or promoting tumor progression. This dichotomy is thought to depend on the intracellular NO concentration and the cell type in which it is generated. Due to its central role in the metabolism of multiple critical constituents involved in signaling and stress, it is crucial to explore NO's contribution to the metabolic dysfunction of melanoma. This review will discuss many known metabolites linked to NO production in melanoma. We discuss the synthesis of these metabolites, their role in biochemical pathways, and how they alter the biological processes observed in the melanoma tumor microenvironment. The metabolic pathways altered by NO and the corresponding metabolites reinforce its dual role in melanoma and support investigating this effect for potential avenues of therapeutic intervention.