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Topic Review
Chronic Myeloid Neoplasms
Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. 
  • 1.1K
  • 29 Apr 2021
Topic Review
Microbiota Alterations in Pancreatic Cancer
The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and pancreatic cancer (PC) development are not completely clear. An altered microbiota may induce oncogenomic changes, or, on the other hand, cancer mutations may have an impact on microbiota composition. Altered microbiota can also influence drug efficacy in PC chemo- and immunotherapies. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.
  • 1.1K
  • 13 Dec 2021
Topic Review
Neuropeptide Y Peptide Family and Cancer
Peptidergic systems are involved in cancer progression and regulate crucial roles such as cell proliferation, migration, and angiogenesis. Available data on the involvement of neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) and their receptors (YRs) in cancer are updated. The structure and dynamics of YRs and their intracellular signaling pathways are also studied. 
  • 1.1K
  • 14 Jun 2023
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.
  • 1.1K
  • 03 Nov 2020
Topic Review
Immunotherapy of Colorectal Cancer
Immunotherapy has become one of the pillars of treatmemt of Colorectal Cancer. This entry explains what Immune Checkpoint Inhibitors are, how they work and which patients are most likely to benefit from them. You will get an overview of the current (2020) scientific evidence on their efficacy in terms of objective tumor response, progression free survival and overall survival, as well as on safety, adverse effects and potential impact on quality of life indicators. Furthermore, ongoing or planned trials are listed.
  • 1.1K
  • 23 Nov 2020
Topic Review
Tumor Microenvironment in Cancer Metastasis
Metastasis, the process by which cancer cells escape primary tumor site and colonize distant organs, is responsible for most cancer-related deaths. The tumor microenvironment (TME), comprises different cell types, including immune cells and cancer-associated fibroblasts, as well as structural elements, such as collagen and hyaluronan that constitute the extracellular matrix (ECM). 
  • 1.1K
  • 08 May 2021
Topic Review
Diffuse Large B-Cell Lymphomas
Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. The term DLBCL reflects the growth pattern and size of the neoplastic cells, which tend to diffusely efface the normal structure of the involved organ (most frequently the lymph node) and are provided with a diameter at least twice that of normal lymphocytes. Although during the last few years several distinct clinical-pathological categories of DLBCL have been reported in the literature, which are nowadays listed in the Revised 4th Edition of the WHO Classification of the Tumours of Haematopoietic and Lymphoid Tissues, about 80% of DLBCLs do not enter into any of these categories and are therefore termed not otherwise specified (NOS). DLBCL-NOS displays a quite variable morphology and only rarely consists of only one cytotype (centroblastic, immunoblastic or anaplastic). Thus, microscopic examination fails to define the cell of origin, prognostic indicators and novel potential therapeutic targets. The standard of care  is the immuno-chemotherapy R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which cures up to 65% of patients. The remaining individuals with DLBCL-NOS experience resistant or relapsing disease and eventually die of it. This situation has promoted a huge number of studies focusing on the pathobiology of the tumour and based on high-throughput techniques, including gene expression profiling and next generation sequencing. In addition, attention has been focused on the mcroenvironmental composition, which can influence the behaviour and response to therapy of the tumour in conjunction with the molecular characteristics of neoplastic cells. The aim of the present review is to discuss the most recent acquisitions in the field of DLBCL-NOS based on the extensive application of molecular techniques, which paves the way to a more rational classification of the tumour along with the identification of effective prognostic indicators and novel therapeutic targets for  ad hoc personalised approaches. 
  • 1.0K
  • 23 Jun 2021
Topic Review
Hypoxia in Lung Cancer Management
Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice.
  • 1.0K
  • 22 Sep 2021
Topic Review
Tumor Microenvironment and Metabolism
There is a growing appreciation that the cells of the tumor microenvironment interact via variations in their dynamic regulation of mitochondrial function. The melatonergic pathway is a core aspect of mitochondrial function, with tumors 'domineering' the homeostasis established in the tumor microenvironment by regulating the core functioning of other cells. This is predominantly achieved by regulating the levels of melatonin and its immediate precursor, N-acetylserotonin (NAS). Applying melatonin to any tumor drives tumor death via apoptosis, whilst NAS can activate the trophic receptor, TrkB, to increase the survival and proliferation of tumors. Given such contrasting effects of melatonin and NAS, it is crucial for tumors to regulate the NAS/melatonin ratio within the tumor microenvironment. Two immune cells can readily kill cancer cells, namely natural killer (NK) cells and CD8+ t cells. The tumor inactivates these cells by releasing kynurenine, which activates the aryl hydrocarbon receptor (AhR) on these immune cells, leading to their inactivation ('exhaustion'), with AhR activation also increasing the NAS/melatonin ratio. NAS release enhances the survival and proliferation of cancer stem-like cells, thereby driving tumor maintenance and spread (metastasis). The cells that can readily kill cancer cells are therefore turned into providers of support for tumor survival and spread. This is achieved via the tumor's regulation of the mitochondrial melatonergic pathway. Similar tumor interactions with the mitochondrial melatonergic pathway allows the tumor to regulate other cells in the tumor microenvironment, as well as influencing how these cells interact with each other. This is predominantly achieved by the altered metabolism and mitochondrial function in the tumor shaping the mitochondrial function of other cells in the tumor microenvironment. As mitochondria evolved over evolution from ancient bacteria, these interactions across cell types in the tumor microenvironment may be viewed as evolutionary modified bacteria dynamically interacting with each other within a quest to achieve 'dominance' via the regulation of mitochondrial melatonergic pathway. This is a novel conceptualization of the tumor microenvironment that emphasizes core metabolic processes, and their regulation by the melatonergic pathway. As a frame of reference this allows the incorporation of previously disparate pieces of data on the tumor microenvironment and also provides a clearer pathway to new research, coupled to treatment implications. 
  • 1.0K
  • 05 Jan 2023
Topic Review
Cancer Photodynamic Therapy
The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions.
  • 1.0K
  • 02 Mar 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.
  • 1.0K
  • 21 Oct 2022
Topic Review
Primary cilia and cancer
Primacy cilia are antenna-like structures present in many vertebrate cells. These organelles detect extracellular cues, transduce signals into the cell, and play an essential role in ensuring correct cell proliferation, migration, and differentiation in a spatiotemporal manner. Not surprisingly, dysregulation of primary cilia can cause various diseases, including cancer. The structure and function of primary cilia are dynamically regulated through many proteins and various posttranslational mechanisms of these proteins, including phosphorylation, acetylation, and ubiquitination. Targeting these signaling that regulates the assembly and disassembly of primary cilia may be a promising approach for cancer treatment.
  • 1.0K
  • 27 Aug 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. 
  • 1.0K
  • 22 Sep 2021
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.
  • 1.0K
  • 13 Jan 2022
Topic Review
The Gut Microbiome and Colorectal Cancer
Colorectal cancer (CRC) represents a significant global health burden, ranking as the third most common cancer and the second leading cause of cancer-related deaths worldwide. The gut microbiome, composed of trillions of commensal microorganisms, plays a vital role in maintaining homeostasis and overall health. Mounting evidence suggests that alterations in the gut microbiome, referred to as dysbiosis, may contribute to the initiation and progression of CRC by modulating the tumor microenvironment (TME), including the tumor stroma.
  • 1.0K
  • 05 Sep 2023
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. 
  • 1.0K
  • 13 Apr 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.
  • 1.0K
  • 26 Oct 2020
Topic Review
Cytokine Networks in Brain Metastases
Brain metastases are the most common of all intracranial tumors and a major cause of death in patients with cancer. Cytokines, including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors are key regulators in the formation of brain metastases. They regulate the infiltration of different cellular subsets into the tumor microenvironment and affect the thera-peutic outcomes in patients.
  • 1.0K
  • 19 Jan 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.
  • 1.0K
  • 23 Jun 2021
Topic Review
Splice Site Selection Abrogated in Cancer
Splicing and alternative splicing (AS) must be tightly regulated, as they have profound effects on gene expression. Various cis-regulatory elements control the fidelity and efficiency of splicing. These include the 5′ and 3′ splice sites (SSs), splicing enhancers, splicing silencers, branch points, and polypyrimidine tracts. A quality control mechanism of splice site selection termed Suppression of Splicing (SOS), was proposed to protect cells from splicing at the numerous intronic unused, latent 5′ splice sites (LSSs) sequences, which are not used under normal growth condition. However, under stress and in cancer thousands of LSSs are activated in splicing resulting in the expression of thousands of aberrant nonsense mRNAs that may be toxic to cells. 
  • 1.0K
  • 20 Jun 2022
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