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Topic Review
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)
Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant genetic disorder associated with an increased lifetime risk of developing colorectal cancer (CRC) (30–73%), endometrial carcinoma (EC) (30–51%) and, less frequently, other malignancies such as gastric, ovarian, urinary tract, pancreatic, small bowel, biliary tract, brain, and skin sebaceous cancers.
  • 999
  • 27 Mar 2023
Topic Review
Contribution of Epstein–Barr Virus to Cancer Hallmarks
The concept of ‘hallmarks of cancer’ was first introduced by Hanahan and Weinberg in 2000 and represented the cellular traits through which different cancers acquire the capabilities to survive, proliferate and disseminate. Epstein–Barr virus (EBV), the first recognized human oncogenic virus in history, is one of the environmental factors that can drive oncogenesis of several lymphoid and epithelial malignancies through various hallmarks of cancer. This entry summarizes the contribution of EBV lytic proteins to cancer hallmarks and provide a framework to address the complexity of EBV-driven oncogenesis.
  • 999
  • 10 Apr 2023
Topic Review
GOF Mutant p53 in Cancers
TP53 is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential. They can inhibit any remaining WTp53 in a dominant negative manner, or they can acquire new functions that promote tumour growth, invasion, metastasis and chemoresistance.
  • 998
  • 17 Nov 2022
Topic Review
The Metastatic Capacity of Melanoma
Metastasization is a multistep process in which cancer cells detach from the primary tumor (or other metastases) and spread to locoregional or distant lymph nodes, or to non-contiguous secondary sites. Here, if the tissue microenvironment allows them to survive, they generate a new tumor.
  • 997
  • 21 Oct 2021
Topic Review
Dendritic Cell Vaccines for Cancer Immunotherapy
Dendritic cells (DCs) are a class of bone-marrow-derived cells present in blood, epithelial, interstitial and lymphoid tissues, originated from lympho-myeloid hematopoiesis through a series of differentiation processes. Throughout the last decades, DC-based anti-tumor vaccines have proven to be a safe therapeutic approach, although with inconsistent clinical results. The functional limitations of ex vivo monocyte-derived dendritic cells (MoDCs) commonly used in these therapies are one of the pointed explanations for their lack of robustness. Among characterized human DC subpopulations, conventional type 1 DCs (cDC1) have emerged as a highly desirable tool for empowering anti-tumor immunity. This DC subset excels in its capacity to prime antigen-specific cytotoxic T cells and to activate natural killer (NK) and natural killer T (NKT) cells, which are critical factors for an effective anti-tumor immune response.
  • 997
  • 29 Mar 2022
Topic Review
IPSC-Based PDAC Models and Immunotherapies
Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex tumor microenvironment (TME) are likely culprits for therapy refractoriness in PDAC. Induced pluripotent stem cells (iPSCs) should be explored as a means to advance the treatment options for PDAC, by providing representative in vitro models of pancreatic cancer development. In addition, iPSCs could be used for tailor-made cellular immunotherapies or as a source of tumor-associated antigens in the context of vaccination.
  • 997
  • 29 Mar 2022
Topic Review
Gal-9/TIM-3 Immune Checkpoint with α-Lactose
The disaccharide lactose is an excipient commonly used in pharmaceutical products. The two anomers, α- and β-lactose (α-L/β-L), differ by the orientation of the C-1 hydroxyl group on the glucose unit. In aqueous solution, a mutarotation process leads to an equilibrium of about 40% α-L and 60% β-L at room temperature.
  • 996
  • 04 Jan 2022
Topic Review
Breast Cancer Biomarkers From Peripheral Blood Cells
While tissue-specific biomarkers, including immune-cell infiltration of the tumor, atypical cells, changes in tumor gene expression, and other malignant changes can serve as reliable cancer biomarkers, they have certain limitations. For instance, the invasiveness of biopsy acquisition makes tissue-specific biomarkers ill-fitted for the real-time monitoring of treatment response. Additionally, while tumor-infiltrating lymphocytes (TILs) may be powerful prognostic biomarkers and have significant predictive value in identifying patients with the highest likelihood of responding to therapy, they are not useful for the early detection of cancer or for cancer screening in people with no symptoms. Less invasive and more easily accessible methods of biological sample acquisition, such as blood collection, can make early detection more feasible and may increase acceptance among patients, thereby leading to potentially faster diagnosis. Need to focus on circulating blood cell transcriptome as a source of breast cancer (BC) biomarkers.
  • 996
  • 12 Apr 2022
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. 
  • 995
  • 22 Sep 2021
Topic Review
ING Genes in NSCLC
Carcinogenic mutations allow cells to escape governing mechanisms that commonly inhibit uncontrolled cell proliferation and maintain tightly regulated homeostasis between cell death and survival. Members of the inhibition of growth (ING) family act as tumor suppressors, governing cell cycle, apoptosis and cellular senescence. The molecular mechanism of action of ING genes, as well as their anchor points in pathways commonly linked to malignant transformation of cells, have been studied with respect to a variety of cancer specimens.
  • 995
  • 23 Aug 2021
Topic Review
Malignant Pleural Mesothelioma
Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets.
  • 994
  • 07 Apr 2021
Topic Review
Near Infrared Photoimmunotherapy
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses an antibody-photoabsorber (IRDye700DX) conjugate (APC) that is activated by NIR light irradiation. A major benefit of NIR-PIT is that only APC-bound cancer cells that are exposed to NIR light are killed by NIR-PIT; thus, minimal damage occurs in adjacent normal cells. NIR-PIT has now been applied to many cancers expressing various cell-surface target proteins using monoclonal antibodies designed to bind to them. Moreover, NIR-PIT is not limited to tumor antigens but can also be used to kill specific host cells that create immune-permissive environments in which tumors grow. Moreover, multiple targets can be treated simultaneously with NIR-PIT using a cocktail of APCs. NIR-PIT has great potential to treat a wide variety of cancers by targeting appropriate tumor cells, immune cells, or both, and can be augmented by other immunotherapies. 
  • 994
  • 23 Jun 2021
Topic Review
Diffuse Intrinsic Pontine Gliomas
Diffuse intrinsic pontine gliomas are malignant brain tumors which arise from the pons in children. These tumors are incurable and nearly all the patients die within a year after diagnosis. 
  • 993
  • 19 Apr 2021
Topic Review
Immuno-PET
“Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. 
  • 992
  • 06 May 2021
Topic Review
DPP-IV Inhibition in Anticancer Treatment
Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nevertheless, the modulation of the bioavailability and function of other DPP-IV substrates, including chemokines, raises the possibility that the use of these orally administered drugs with favorable side-effect profiles might be extended beyond the treatment of hyperglycemia. 
  • 992
  • 05 May 2022
Topic Review
CTLA-4
Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are limited at the moment to a minority of patients and there is a need for a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind with higher affinity to CD80 and CD86 than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap. 
  • 991
  • 13 Apr 2021
Topic Review
Orexins/Hypocretins and Cancer
Orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role.
  • 991
  • 03 Sep 2021
Topic Review
Chimeric Antigen Receptor T cells in Multiple Myeloma
Multiple myeloma is a disease of malignant plasma cells and the second most common hematological cancer. This entry describes the history and use of CAR-T cells for the treatment of this disease as well as comment on future approaches.
  • 991
  • 03 Dec 2021
Topic Review
Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma
Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Using targeted drugs to disrupt interactions between these cells which can support cancer cell growth, invasion, and immune suppression has become an important area of exploration in the pancreatic cancer field.  Pancreatic ductal adenocarcinoma (PDAC) is the most common histology of pancreatic cancer, representing >85% of all pancreatic cancer diagnoses.
  • 991
  • 08 Sep 2022
Topic Review
Metabolomics-Microbiome Crosstalk in Breast Cancer Microenvironment
The human microbiome is defined as the full array of the diverse microorganisms (microbiota) that live on and in humans, as well as their genetic materials. It is considered one of the leading environmental factors in disease development, with Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria dominant species. Human microbiota manifestation is influenced by multiple environmental and physiological changes, including age, sex, race, geography, diet, host genetics and lifestyle, drugs like antibiotics, and interaction with the immune system and metabolic pathway.
  • 989
  • 11 Nov 2021
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