Relationship of Signaling Pathways between RKIP Expression and the Inhibition of EMT-Inducing Transcription Factors SNAIL1/2, TWIST1/2 and ZEB1/2.

Untreated primary carcinomas often lead to progression, invasion and metastasis, a process that involves the epithelial-to-mesenchymal transition (EMT). Several transcription factors (TFs) mediate the development of EMT, including SNAIL1/SNAIL2, TWIST1/TWIST2 and ZEB1/ZEB2, which are overexpressed in various carcinomas along with the under expression of the metastasis suppressor Raf Kinase Inhibitor Protein (RKIP). Overexpression of RKIP inhibits EMT and the above associated TFs.

The Role of TAMs in the Regulation of Tumor Cell Resistance to Chemotherapy.

Tumor-associated macrophages (TAMs) are the predominant cell infiltrate in the immunosuppressive tumor microenvironment (TME). TAMs are central to fostering pro-inflammatory conditions, tumor growth, metastasis, and inhibiting therapy responses. Many cancer patients are innately refractory to chemotherapy and or develop resistance following initial treatments.

Polarization of M2 Tumor-Associated Macrophages (TAMs) in Cancer Immunotherapy.

We have witnessed in the last decade new milestones in the treatment of various resistant cancers with new immunotherapeutic modalities. These advances have resulted in significant objective durable clinical responses in a subset of cancer patients. These findings strongly suggested that immunotherapy should be considered for the treatment of all subsets of cancer patients.

Targeting the Depletion of M2 Macrophages: Implication in Cancer Immunotherapy.

We have witnessed the emergence of immunotherapy against various cancers that resulted in significant clinical responses and particularly in cancers that were resistant to chemotherapy. These milestones have ignited the development of novel strategies to boost the anti-tumor immune response for immune-suppressed tumors in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant cells in the TME, and their frequency correlates with poor prognosis.

Immune Evasion in Cancer Is Regulated by Tumor-Asociated Macrophages (TAMs): Targeting TAMs.

Recent advancements in cancer treatment have explored a variety of approaches to address the needs of patients. Recently, immunotherapy has evolved as an efficacious treatment for various cancers resistant to conventional therapies. Hence, significant milestones in immunotherapy were achieved clinically in a large subset of cancer patients.

Therapeutic Implications of Targeting YY1 in Glioblastoma.

The transcription factor Yin Yang 1 (YY1) plays a pivotal role in the pathogenesis of glioblastoma multiforme (GBM), an aggressive form of brain tumor. This review systematically explores the diverse roles of YY1 overexpression and activities in GBM, including its impact on the tumor microenvironment (TME) and immune evasion mechanisms. Due to the poor response of GBM to current therapies, various findings of YY1-associated pathways in the literature provide valuable insights into novel potential targeted therapeutic strategies.

Cross-Talks between Raf Kinase Inhibitor Protein and Programmed Cell Death Ligand 1 Expressions in Cancer: Role in Immune Evasion and Therapeutic Implications.

Innovations in cancer immunotherapy have resulted in the development of several novel immunotherapeutic strategies that can disrupt immunosuppression. One key advancement lies in immune checkpoint inhibitors (ICIs), which have shown significant clinical efficacy and increased survival rates in patients with various therapy-resistant cancers. This immune intervention consists of monoclonal antibodies directed against inhibitory receptors (e.

Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1.

During the last decade, we have witnessed several milestones in the treatment of various resistant cancers including immunotherapeutic strategies that have proven to be superior to conventional treatment options, such as chemotherapy and radiation. This approach utilizes the host's immune response, which is triggered by cancer cells expressing tumor-associated antigens or neoantigens. The responsive immune cytotoxic CD8 T cells specifically target and kill tumor cells, leading to tumor regression and prolongation of survival in some cancers; however, some cancers may exhibit resistance due to the inactivation of anti-tumor CD8 T cells.

Historical Perspectives of the Role of NO/NO Donors in Anti-Tumor Activities: Acknowledging Dr. Keefer's Pioneering Research.

The role of nitric oxide (NO) in cancer has been a continuous challenge and particularly the contradictory findings in the literature reporting NO with either anti-cancer properties or pro-cancer properties. This dilemma was largely resolved by the level of NO/inducible nitric oxide synthase in the tumor environment as well as other cancer-associated gene activations in different cancers. The initial findings on the role of NO as an anti-cancer agent was initiated in the late 1990's in Dr.

Role of YY1 in the Regulation of Anti-Apoptotic Gene Products in Drug-Resistant Cancer Cells.

Cancer is a leading cause of death among the various diseases encountered in humans. Cancer is not a single entity and consists of numerous different types and subtypes that require various treatment regimens. In the last decade, several milestones in cancer treatments were accomplished, such as specific targeting agents or revitalizing the dormant anti-tumor immune response.

Cancer Resistance Is Mediated by the Upregulation of Several Anti-Apoptotic Gene Products the Inducible Nitric Oxide Synthase/Nitric Oxide Pathway: Therapeutic Implications.

Several therapeutic strategies for cancer treatments have been developed with time, and significant milestones have been achieved recently. However, with these novel therapies, not all cancer types respond and in the responding cancer types only a subset is affected. The failure to respond is principally the result that these cancers develop several mechanisms of resistance.

Cancer resistance via the downregulation of the tumor suppressors and expressions: therapeutic implications.

The Raf kinase inhibitor protein (RKIP) has been reported to be underexpressed in many cancers and plays a role in the regulation of tumor cells' survival, proliferation, invasion, and metastasis, hence, a tumor suppressor. RKIP also regulates tumor cell resistance to cytotoxic drugs/cells. Likewise, the tumor suppressor, phosphatase and tensin homolog (PTEN), which inhibits the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, is either mutated, underexpressed, or deleted in many cancers and shares with RKIP its anti-tumor properties and its regulation in resistance.

RKIP: A Pivotal Gene Product in the Pathogenesis of Cancer.

Raf kinase inhibitor protein (RKIP), previously known as a phosphatidylethanolamine-binding protein (PEBP), was cloned by Yeung et al [...

The Role of RKIP in the Regulation of EMT in the Tumor Microenvironment.

The Raf Kinase Inhibitor Protein (RKIP) is a unique gene product that directly inhibits the Raf/Mek/Erk and NF-kB pathways in cancer cells and resulting in the inhibition of cell proliferation, viability, EMT, and metastasis. Additionally, RKIP is involved in the regulation of cancer cell resistance to both chemotherapy and immunotherapy. The low expression of RKIP expression in many cancer types is responsible, in part, for the pathogenesis of cancer and its multiple properties.

Long non-coding RNAs (lncRNAs) signaling in cancer chemoresistance: From prediction to druggability.

The acquisition of cancer cell resistance to conventional chemotherapeutics is considered the major driver of treatment failure and disease recurrence in most solid and hematological malignancies. The molecular basis of tumor chemoresistance has been extensively investigated and newly identified gene signatures have eventually paved the way towards the development of novel therapeutic interventions in the era of precision medicine in oncology. Long non-coding RNAs (lncRNAs) are defined as a class of transcripts longer than 200 nucleotides that lack translational activities and are highly abundant across the human genome.

The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis.

The expression of inducible nitric oxide synthase (iNOS; NOS2) and derived NO in various cancers was reported to exert pro- and anti-tumorigenic effects depending on the levels of expression and the tumor types. In humans, the breast cancer level of iNOS was reported to be overexpressed, to exhibit pro-tumorigenic activities, and to be of prognostic significance. Likewise, the expression of the oncogenes HER2, BRCA1, and BRCA2 has been associated with malignancy.

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer.

Lung cancer (LC) represents a global threat, being the tumor with the highest mortality rate. Despite the introduction of novel therapies (e.g.

Targeting the V-Type Immunoglobulin Domain-Containing Suppressor to T Cell Activation (VISTA) with Agonist Monoclonal Antibodies in Autoimmunity.

The recognition of self-antigens by the T-cell immune system can results in autoimmunity. Current treatments of autoimmunity include non-steroid anti-inflammatory drugs and treatments aimed to control the immune system directly. Additionally, inhibiting signaling pathways that encourage T cell activation are promising strategies to help increase self-tolerance and control the inflammatory immune response.

RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity.

Several gene products play pivotal roles in the induction of inflammation and the progression of cancer. The Raf kinase inhibitory protein (RKIP) is a cytosolic protein that exerts pleiotropic activities in such conditions, and thus regulates oncogenesis and immune-mediated diseases through its deregulation. Herein, we review the general properties of RKIP, including its: (i) molecular structure; (ii) involvement in various cell signaling pathways (i.

Regulation of T Cells in Cancer by Nitric Oxide.

The T cell-mediated immune response is primarily involved in the fight against infectious diseases and cancer and its underlying mechanisms are complex. The anti-tumor T cell response is regulated by various T cell subsets and other cells and tissues in the tumor microenvironment (TME). Various mechanisms are involved in the regulation of these various effector cells.