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Topic Review
Circular RNAs (CircRNAs)
CircRNAs are a recently discovered class of ncRNA molecules. They are formed during the process of RNA transcript maturation. Structurally, circRNAs are covalently closed by a connection between a downstream donor and upstream acceptor RNA splice sites linked by a phosphodiester bond.
  • 1.0K
  • 29 Nov 2023
Topic Review
ADGRG1/GPR56 in Tumor Progression
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. 
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  • 16 Dec 2021
Topic Review
Modeling Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are revolutionizing the treatment of cancer, but models that accurately predict their efficacy before administering them to humans are badly needed.  This entry presents the application of a microfluidic tumor model that simulates the interactions between immune cells and tumors in a dynamic microenvironment, utilizing real-time imaging and image analytic algorithms to demonstrate excellent correlations between the laboratory model and animal studies.  Future applications of the system in precision medicine will explore the use of the device for selecting patient-specific therapies for cancer.
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  • 26 Oct 2020
Topic Review
Cholesterol Biosynthesis and Breast Cancer Initiation and Development
Cholesterol (CHOL) is a multifaceted lipid molecule. It is an essential structural component of cell membranes, where it cooperates in regulating the intracellular trafficking and signaling pathways. Additionally, it serves as a precursor for vital biomolecules, including steroid hormones, isoprenoids, vitamin D, and bile acids. Although CHOL is normally uptaken from the bloodstream, cells can synthesize it de novo in response to an increased requirement due to physiological tissue remodeling or abnormal proliferation, such as in cancer. Cumulating evidence indicated that increased CHOL biosynthesis is a common feature of breast cancer and is associated with the neoplastic transformation of normal mammary epithelial cells.
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  • 29 Feb 2024
Topic Review
Immunoproteasome
Proteasome inhibition is a promising strategy for the treatment of multiple myeloma; unfortunately, this disease is often associated with an increasing chemoresistance. One novel approach may be to target the immunoproteasome, a proteasomal isoform mainly present in cells of hematopoietic origin. We investigated the activity of a panel of amides against immunoproteasome core particles as potential agents for the treatment of multiple myeloma (MM). Amide 6 showed an ideal profile since it was able to inhibit both the chymotrypsin-like activities of the immunoproteasome with Ki values of 4.90 µM and 4.39 µM for β1i and β5i, respectively, coupled with an EC50 =17.8 µM against MM.1R cells. Compound 6 inhibited also ubiquitinated protein degradation and was able to act on different phases of MM cell cycle reducing the levels of cyclin A/CDK1, cyclin B/CDK1 and cyclin D/CDK4/6 complexes, which turns in cell cycle arrest.
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  • 03 Nov 2020
Topic Review
Protein Variants in Cancer-Related Genes
Large scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this entry we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and function was experimentally determined. We collected a set of 164 variants from 11 proteins to analyze the impact of missense mutations at structural and functional levels, and to assess the performance of state-of-the-art methods (FoldX and Meta-SNP) for predicting protein stability change and pathogenicity. 
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  • 22 Sep 2021
Topic Review
Necroptosis and Prostate Cancer
Necroptosis is a programmed form of necrosis characterized by mitochondrial alterations and plasma membrane permeabilization resulting in the release of cytoplasmic content into extracellular space, and leading to inflammatory reactions. Besides its critical role in viral defense mechanisms and inflammatory diseases, necroptosis plays pivotal functions in the drug response of tumors, including prostate cancer. Necroptosis is mainly governed by kinase enzymes, including RIP1, RIP3, and MLKL, and conversely to apoptosis, is a caspase-independent mechanism of cell death. Numerous compounds induce necroptosis in prostate cancer models, including (i) compounds of natural origin, (ii) synthetic and semisynthetic small molecules, and (iii) selenium and selenium-based nanoparticles.
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  • 13 Apr 2022
Topic Review
Therapy-Related MN and Clonal Hematopoiesis
In the last decades the improved management of cancer patients and the overall prolonged life expectancy contributed to the increased number of patients at risk of late clonal events such as therapy-related myeloid neoplasms (t-MN). The discovery of clonal hematopoiesis of indeterminate potential (CHIP) in normal individuals has shed light on the pathophysiologic mechanism behind the process of myeloid evolution, defining CHIP carriers at higher risk of progression. Moreover, different patterns of clonal evolution have been identified in case of t-MN development after anti-cancer treatment exposure. 
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  • 22 Apr 2021
Topic Review
Clinical Applications of Short Non-Coding RNA-Based Therapies
RNA therapies have demonstrated clinical potential for both the treatment of cancer and other pathologies. Therapeutic delivery and resulting adverse events remain significant roadblocks in implementing many of these drugs into clinical practice, but the FDA approval of three Alnylam Pharmaceuticals’ small interfering RNAs (siRNAs) therapies has been a milestone in developing therapies tailored to disease-driving target genes. While it seems that RNAs can be administered “naked” in closed-compartment organs such as eyes and lungs, more research is needed for systemic administration. Lipid nanoparticles represent a promising delivery method, but some challenges remain because of their potential to elicit an immune response, relatively low circulation times, and relatively large size. The use of GalNAc for the delivery and targeting of siRNAs has made significant progress, but delivery systems targeted to organs other than the liver would broaden the range of diseases that could be treated with RNA therapies.
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  • 07 Apr 2022
Topic Review
Structure Dynamics and Signaling of the Neurokinin-1 Receptor
Substance P (SP), the first isolated neuropeptide, belongs to the family of tachykinin peptides and is the natural ligand of neurokinin-1 receptors (NK-1R), also named SP receptors. The undecapeptide activates the receptor after specifically binding to the protein and triggers intracellular signals leading to different biochemical events and subsequent physiological responses. 
  • 1.0K
  • 21 Oct 2022
Topic Review
Cancer Treatment and Immunotherapy during Pregnancy
According to McCormik and Peterson (2018), the most common cancers of reproductive age in women are melanoma, breast cancer (the most common gestational cancer and reaches 20% of cases), thyroid cancer, cervical cancer, and lymphomas (most commonly Hodgkin’s lymphoma). A pregnancy that coexists with cancer is not an ordinary pregnancy and consists of a complex medical condition. In the majority of these cases, various therapeutic and ethical dilemmas arise.
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  • 21 Oct 2022
Topic Review
HLA-I and Cancer Derived Extracellular Vesicles
The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign cancer-related antigenic peptides has recently been highlighted by the successful application of monoclonal antibody-based checkpoint inhibitors as novel immune therapies. Thus, there is an increased interest in fully characterising the repertoire of peptides that are being presented to cytotoxic CD8+ T cells by cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all cancer cells. Whilst the peptide ligandome presented by cell surface HLA class I molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined.
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  • 13 Jan 2022
Topic Review
Hilar Biliary Obstruction
Malignant hilar biliary obstruction (HBO) represents a complex clinical condition in terms of diagnosis, surgical and medical treatment, endoscopic approach, and palliation. The main etiology of malignant HBO is hilar cholangiocarcinoma that is considered an aggressive biliary tract’s cancer and has still today a poor prognosis.
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  • 18 Mar 2021
Topic Review
P53 Dysfunction in Colorectal Cancer
Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling.
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  • 23 Jun 2021
Topic Review
Promising Biomarkers of RILI
Radiation-induced lung injury (RILI) is one of the main dose-limiting side effects in patients with thoracic cancer during radiotherapy. No reliable predictors or accurate risk models are currently available in clinical practice. Severe radiation pneumonitis (RP) or pulmonary fibrosis (PF) will reduce the quality of life, even when the anti-tumor treatment is effective for patients. Since the clinical symptoms or imaging changes identifying toxicity do not appear in the early stage, ideal biomarkers are crucial for early diagnosis and intervention in order to prevent lung complications.
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  • 26 Sep 2021
Topic Review
Myeloma–Bone Interaction
Multiple myeloma (MM) has a propensity to develop preferentially in bone and form bone-destructive lesions. MM cells enhance osteoclastogenesis and bone resorption through activation of the RANKL–NF-κB signaling pathway while suppressing bone formation by inhibiting osteoblastogenesis from bone marrow stromal cells (BMSCs) by factors elaborated in the bone marrow and bone in MM, including the soluble Wnt inhibitors DKK-1 and sclerostin, activin A, and TGF-β, resulting in systemic bone destruction with loss of bone. Osteocytes have been drawn attention as multifunctional regulators in bone metabolism. MM cells induce apoptosis in osteocytes to trigger the production of factors, including RANKL, sclerostin, and DKK-1, to further exacerbate bone destruction. Bone lesions developed in MM, in turn, provide microenvironments suited for MM cell growth/survival, including niches to foster MM cells and their precursors. 
  • 1.0K
  • 27 Oct 2021
Topic Review
Cancer Metastasis
Despite great advances in the detailed profiling of tumor cells and the development of therapeutic agents, cancer metastasis is still a big hurdle in the treatment of cancer patients. This is possibly because tumor cells plastically evolve through interplay with the host environment, including stromal cells, vascular cells, and immune cells. The reciprocal evolution among the numerous components further increases the heterogeneity and complexity in both tumor cells and the host, leading to refractory cancer. It is important to better understand the entire metastatic cascade and the practical implementations targeting the oncoimmune drivers in the mechanisms.
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  • 24 Feb 2021
Topic Review
Abscopal Effect
The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation.
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  • 17 Nov 2021
Topic Review
IDH Mutations in Chondrosarcoma
Chondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (IDH) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in later stages remains ambiguous. The prognostic value of the IDH mutation in chondrosarcoma seems controversial and (pre)clinical studies that have focused on the direct and indirect targeting of the IDH mutation have not yielded novel treatment strategies.
  • 1.0K
  • 21 Aug 2023
Topic Review
CN133
Pediatric ependymoma (EPN) is a highly aggressive tumor of the central nervous system that remains incurable in 40% of cases. In children, the majority of cases develop in the posterior fossa and can be classified into two distinct molecular entities: EPN posterior fossa A (PF-EPN-A) and EPN posterior fossa B (PF-EPN-B). Patients with PF-EPN-A have poor outcome and are in demand of new therapies. In general, PF-EPN-A tumors show a balanced chromosome copy number profile and have no recurrent somatic nucleotide variants. However, these tumors present abundant epigenetic deregulations, thereby suggesting that epigenetic therapies could provide new opportunities for PF-EPN-A patients. In vitro epigenetic drug screening of 11 compounds showed that histone deacetylase inhibitors (HDACi) had the highest anti-proliferative activity in two PF-EPN-A patient-derived cell lines. Further screening of 5 new brain-penetrating HDACi showed that CN133 induced apoptosis in vitro, reduced tumor growth in vivo and significantly extended the survival of mice with orthotopically-implanted EPN tumors by modulation of the unfolded protein response, PI3K/Akt/mTOR signaling, and apoptotic pathways among others.
  • 1.0K
  • 09 Apr 2021
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