Topic Review
DYRK kinase family in cancer
       DYRK (dual-specificity tyrosine-regulated kinases) are an evolutionary conserved family of protein kinases with members from yeast to humans. In humans, DYRKs are pleiotropic factors that phosphorylate a broad set of proteins involved in many different cellular processes, including those associated with all the hallmarks of cancer. In accordance with an involvement of DYRK kinases in the regulation of tumorigenic processes, an increasing number of research studies are showing either alterations of DYRK gene expression in tumor samples and/or providing evidence of DYRK-dependent mechanisms that contribute to tumor initiation and/or progression.
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  • 28 Aug 2020
Topic Review
Tumor Microenvironment in melanoma
Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase (MEK), v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.
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  • 21 Oct 2020
Topic Review
Myokine Irisin in Cancer
Regular exercise/physical activity is beneficial for the health of an individual and lowers the risk of getting different diseases, including cancer. How exactly exercise results in these health benefits is not known. Recent studies suggest that the molecule irisin released by muscles into the blood stream after exercise may be responsible for these effects.
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  • 17 Jun 2021
Topic Review
Immunogenic Cell Death in Cancer
Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD).
  • 1.1K
  • 25 Dec 2020
Topic Review
Melatonin in the Epithelial-to-Mesenchymal Transition in Cancer
The epithelial-to-mesenchymal transition (EMT) is a process taking place during carcinogenesis. The phenotypic changes include the acquisition of new properties such as increased motility and polarity, leading to invasiveness and the formation of metastasis and chemo- and radioresistance. During the process, epithelial markers are lost whilst mesenchymal markers are overexpressed. EMT-related transcription factors are induced and multiple signaling pathways are activated. Several microRNAs are altered during the transition. Many of these molecules are regulated by melatonin, the pineal hormone, thus behaving as an inhibitor of the EMT in cancer progression. 
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  • 12 Mar 2024
Topic Review
EphA2 Signaling in tumors
The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC). EphA2 is involved in tumor progression and resistance to therapy.
  • 1.1K
  • 18 Mar 2021
Topic Review
HDAC6
Histone deacetylase (HDAC) 6 is a zinc-dependent enzyme of HDAC class IIb. HDAC6 is unique within the HDAC family due to a particular structure giving it unique biological functions implicated in all major cell pathways. This isoenzyme is mainly active in the cytoplasm and possesses two functional catalytic sites and an ubiquitin-binding domain. The deacetylase functions of HDAC6 targets multiple substrates including essentially α-tubulin and heat shock protein (HSP)90α which are key factors in cell regulatory networks through the regulation of the microtubule network and many protein functions, respectively. Accordingly, several studies have highlighted the role of HDAC6 in various pathological conditions. For instance HDAC6 overexpression frequently correlates with tumorigenesis and favor cell survival and metastasis. Therefore, HDAC6 represents an interesting potential therapeutic target.
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  • 15 Jul 2021
Topic Review
Antioxidant of Dietary Vitamins A, C, and E
Non-enzymatic antioxidants, which include vitamin A, vitamin C, and vitamin E, are commonly used dietary supplements for general health purposes. Given their safe profile and potential link with a decreased risk of cancer, they represent an attractive option as preventive anti-cancer agents.
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  • 03 Apr 2023
Topic Review Video Peer Reviewed
Flash Radiotherapy: Innovative Cancer Treatment
Flash radiotherapy (Flash-RT) is an innovative technique used in radiotherapy for cancer treatment because it delivers an extremely high dose of radiation (>40 Gy/s) to the tumour in a very short period of time, typically within a fraction of a second. This ultra-fast delivery of radiation distinguishes Flash-RT from conventional radiotherapy, which typically involves the delivery of radiation over a longer time period, often several minutes. Studies conducted in cell and preclinical models suggested that Flash-RT may spare normal tissues from radiation-related side effects, such as skin toxicity, gastrointestinal complications, and damage to organs-at-risk. This is believed to be due to the unique normal tissue response to the ultra-high dose rate. Nevertheless, while Flash-RT shows promising results in preclinical and early clinical studies, one should note that the technique is still in the early stages of development. This entry provides a comprehensive exploration of the immense potentials of Flash-RT, covering its background, mechanisms, radiation sources, recent experimental findings based on cell and preclinical models, and future prospects. It aims to provide valuable insights into this innovative radiotherapy technology for anyone interested in the subject.
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  • 27 Jun 2023
Topic Review
Electroporation based treatments in Urology
The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabilization of cell membrane phospholipids, IRE (as well as other treatments based on EP) provides selectivity sparing extracellular proteins and matrix. Reversible EP enables the transfer of genes, drugs, and small exogenous proteins. In clinical practice, reversible EP can locally increase the uptake of cytotoxic drugs such as cisplatin and bleomycin. This approach is known as electrochemotherapy (ECT). Few in vivo and in vitro trials of ECT have been performed on urological cancers. EP provides the possibility of transmission of genes across the cell membrane. As the protocols of gene electrotransfer (GET) over the last few years have improved, EP has become a well-known technique for non-viral cell transfection. GET involves DNA transfection directly to the cancer or the host skin and muscle tissue. Among urological cancers, the GET of several plasmids encoding prostate cancer antigens has been investigated in clinical trials.
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  • 25 Aug 2020
Topic Review
Targeting PI3K/Akt/mTOR in AML
Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy, characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. While reductions of bulk malignant cells can be achieved in the majority of patients by standard chemotherapy consisting of cell cycle active drugs, such as cytarabine and anthracyclines, approximately two-thirds of patients relapse after the induction therapy, highlighting an unmet need for a more targeted therapeutic approach. A rare population of therapy-resistant cells are believed to be the origin of relapse, termed leukemia stem cells (LSCs), also referred to as leukemia-initiating cells (LICs). These cells acquire enhanced self-renewal capacity and exhibit a block in differentiation.
  • 1.1K
  • 23 Sep 2020
Topic Review
Wnt Signaling in Human Diseases
Wnt signaling has been implicated in a wide spectrum of important biological phenomena, where either a deficiency or overactivation of key effectors can lead to various human diseases. This review highlights historical and recent findings on key mediators of Wnt signaling and its association with various developmental diseases and tumorigenesis.
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  • 13 Nov 2020
Topic Review
Aurora Kinase B in Cancer
Aurora kinase B (AURKB) is a mitotic serine/threonine protein kinase that belongs to the aurora kinase family along with aurora kinase A (AURKA) and aurora kinase C (AURKC). AURKB is a member of the chromosomal passenger protein complex and plays a role in cell cycle progression.
  • 1.1K
  • 23 Jun 2021
Topic Review
Perilipin 5 in NAFLD
Perilipins are a family of five closely related proteins expressed on the surface of lipid droplets (LD) in several tissues acting in several pathways involved in lipid metabolism. Recent studies have shown that Plin5 depletion acts protectively in the pathogenesis of liver injury underpinning the importance of pathways associated with PLIN5. PLIN5 expression is involved in pro-inflammatory cytokine regulation and mitochondrial damage, as well as endoplasmic reticulum (ER) stress, making it critical target of the NAFLD-HCC studies. 
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  • 23 Jun 2021
Topic Review
ROS in the Tumor Microenvironment
Reactive oxygen species (ROS) are important signaling molecules in cancer. The level of ROS will determine physiological effects. While high levels of ROS can cause damage to tissues and cell death, low levels of ROS can have a proliferative effect. ROS are produced by tumor cells but also cellular components that make up the tumor microenvironment (TME).
  • 1.1K
  • 19 Aug 2021
Topic Review
Fyn
Fyn is a non-receptor or cytoplasmatic tyrosine kinase (TK) belonging to the Src family kinases (SFKs) involved in multiple transduction pathways in the central nervous system (CNS) including synaptic transmission, myelination, axon guidance, and oligodendrocyte formation. Almost one hundred years after the original description of Fyn, this protein continues to attract extreme interest because of its multiplicity of actions in the molecular signaling pathways underlying neurodevelopmental as well as neuropathologic events. Fyn is a common factor in healthy and diseased brains that targets different proteins and shapes different transduction signals according to the neurological conditions. In particular, Fyn mediates signaling pathways involved in neuronal differentiation and plasticity that have been subjected to considerable attention lately, opening the fascinating scenario to target Fyn TK for the development of potential therapeutic interventions for the treatment of CNS injuries and certain neurodegenerative disorders like Alzheimer's disease.
  • 1.1K
  • 05 Nov 2020
Topic Review
CYP2D6 and Tamoxifen Metabolism
Tamoxifen is an important adjuvant endocrine therapy in estrogen receptor (ER)-positive breast cancer patients. It is metabolized into its most active antiestrogenic metabolite endoxifen, predominantly by cytochrome P450 2D6 (CYP2D6). Many factors, including genetic variation in CYP2D6, influence tamoxifen metabolism and pharmacokinetics.
  • 1.1K
  • 09 Mar 2021
Topic Review
ZEB Family
Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of EMT mechanism, therefore reducing metastasis. Also, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.
  • 1.1K
  • 19 Jul 2020
Topic Review
Tumour Microenvironment
The totality of normal cells, blood vessels and molecules embedding the tumor cells and sustaining their growth, characterized by a continuous bidirectional reshaping.
  • 1.1K
  • 02 Feb 2021
Topic Review
Tumour Hypoxia
Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. There have been extensive studies to target tumour hypoxia and here are some examples of historical methods as well as new approaches. 
  • 1.1K
  • 03 Nov 2021
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