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Topic Review
Inhibitors Targeting the 80S ribosome
Protein biosynthesis is a vital process for all kingdoms of life. The ribosome is the massive ribonucleoprotein machinery that reads the genetic code, in the form of messenger RNA (mRNA), to produce proteins. The mechanism of translation is tightly regulated to ensure that cell growth is well sustained. In bacteria, the ribosome is a major target of inhibitors, as demonstrated by the high number of small molecules identified to bind to it. In eukaryotes, the design of ribosome inhibitors may be used as a therapy to treat cancer cells, which exhibit higher proliferation rates compared to healthy ones. 
  • 1.6K
  • 28 Sep 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).
  • 1.6K
  • 19 Aug 2021
Topic Review
Polymeric Micelles for Anticancer Hydrophobic Drugs
Cancer has become one of the deadliest diseases in our society. Surgery accompanied by subsequent chemotherapy is the treatment most used to prolong or save the patient’s life. Still, it carries secondary risks such as infections and thrombosis and causes cytotoxic effects in healthy tissues. Using nanocarriers such as smart polymer micelles is a promising alternative to avoid or minimize these problems. These nanostructured systems will be able to encapsulate hydrophilic and hydrophobic drugs through modified copolymers with various functional groups such as carboxyls, amines, hydroxyls, etc.
  • 1.6K
  • 13 Jan 2023
Topic Review
5-ALA Metabolic Pathway
5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 
  • 1.6K
  • 22 Jun 2022
Topic Review
Targeting Gut Microbial Biofilms
Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
  • 1.6K
  • 22 Oct 2020
Topic Review
Proteoglycans in the hormone-dependent cancers
The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Notably, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and its' PG components crucially mediate these processes including cancer metastasis, angiogenesis, immunobiology, autophagy, and response to therapy. Hormone-dependent cancers exhibit high morbidity and mortality. In spite of advances in therapy, the treatment  of hormone-dependent cancers remains an unmet health need. The tumor microenvironment (TME) exhibits unique characteristics that differ among various tumor types. It is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded and supported by components of the extracellular matrix (ECM). Therefore, the interactions among cancer cells, stromal cells, and components of the ECM determine cancer progression and response to therapy. Proteoglycans (PGs), hybrid molecules consisting of a protein core to which sulfated glycosaminoglycan chains are bound, are significant components of the ECM that are implicated in all phases of tumorigenesis. These molecules, secreted by both the stroma and cancer cells, are crucial signaling mediators that modulate the vital cellular pathways implicated in gene expression, phenotypic versatility, and response to therapy in specific tumor types. A plethora of deregulated signaling pathways contributes to the growth, dissemination, and angiogenesis of hormone-dependent cancers. Specific inputs from the endocrine and immune systems are some of the characteristics of hormone-dependent cancer pathogenesis. Importantly, the mechanisms involved in various aspects of cancer progression are executed in the ECM niche of the TME, and the PG components crucially mediate these processes.
  • 1.6K
  • 31 Aug 2020
Topic Review
Advances in Histone Demethylase KDM3A
Lysine-specific histone demethylase 3 (KDM3) subfamily proteins are H3K9me2/me1 histone demethylases that promote gene expression. The KDM3 subfamily primarily consists of four proteins (KDM3A−D). All four proteins contain the catalytic Jumonji C domain (JmjC) at their C-termini, but whether KDM3C has demethylase activity is under debate. In addition, KDM3 proteins contain a zinc-finger domain for DNA binding and an LXXLL motif for interacting with nuclear receptors. Of the KDM3 proteins, KDM3A is especially deregulated or overexpressed in multiple cancers, making it a potential cancer therapeutic target. However, no KDM3A-selective inhibitors have been identified to date because of the lack of structural information. Uncovering the distinct physiological and pathological functions of KDM3A and their structure will give insight into the development of novel selective inhibitors.
  • 1.6K
  • 19 Oct 2020
Topic Review
Chemotherapy Resistance
Multidrug resistance is a major factor contributing to the failure of cancer therapy and poor patient outcomes. While apoptosis (apoptotic cell death) is the desired outcome of anti-cancer therapy, chemotherapy and radiation often induce a number of mechanisms that can mediate resistance. p53 is an essential tumor suppressor and stress response protein, modulating multiple cellular responses to therapy. Gain of function (GOF) p53 mutations have been implicated in increased susceptibility to the development of drug resistance, by compromising wild type anti-tumor functions of p53 or modulating key p53 processes that confer chemotherapy resistance, such as autophagy. Autophagy, a conventionally cytoprotective mechanism, is often a “first responder” to chemotherapy (or radiation), by promoting the removal of damaged organelles and preventing excessive accumulation of damaged proteins; thus, autophagy, via its cytoprotectivefunction, may allow tumor cells to evade apoptotic cell death. However, substantial pre-clinical data and inconsistent clinical efficacy of autophagy inhibitors in combination with cancer chemotherapy indicates that autophagy can exhibit multiple functions and does not act solely as a cytoprotective response. Further inquiry relating to the influence of p53 status on autophagic function and its contributions to multidrug resistance will provide valuable insights towards patient response to therapy and the possibility of developing novel therapeutics for chemosensitization in the face of multidrug resistance. 
  • 1.6K
  • 16 Dec 2020
Topic Review
Cysteine Aminotransferase
The hydrogen sulfide (H2S)-generating enzymatic system composed of cysteine aminotransferase (CAT, EC 2.6.1.3, also known as aspartate aminotransferase, AST, or glutamate transaminase, GOT), and 3-mercaptopyruvate sulfurtransferase (MST, EC 2.8.1.2), is known to be implicated in the catabolism of cysteine [1].
  • 1.6K
  • 27 Oct 2020
Topic Review
Mechanisms of Mitotane Action in Adrenocortical Cancer
Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. 
  • 1.6K
  • 24 Dec 2021
Topic Review
Alkaloids and Their General Applications
Alkaloids are organic chemical compounds with a cyclic ring structure containing one or more basic nitrogen atoms. They are widely distributed in nature and are found as naturally occurring secondary metabolites in both plants and animals.
  • 1.6K
  • 11 Aug 2023
Topic Review
Sphingolipids in Mitophagy and Cancer
Sphingolipids are membrane-associated lipids that are involved in signal transduction pathways regulating cell death, growth, and migration. In cancer cells, sphingolipids regulate pathways relevant to cancer therapy, such as invasion, metastasis, apoptosis, and lethal mitophagy. Notable sphingolipids include ceramide, a sphingolipid that induces death and lethal mitophagy, and sphingosine-1 phosphate, a sphingolipid that induces survival and chemotherapeutic resistance. These sphingolipids participate in regulating the process of mitophagy, where cells encapsulate damaged mitochondria in double-membrane vesicles (called autophagosomes) for degradation. Lethal mitophagy is an anti-tumorigenic mechanism mediated by ceramide, where cells degrade many mitochondria until the cancer cell dies in an apoptosis-independent manner.
  • 1.6K
  • 06 Jun 2021
Topic Review
Nanocarriers Used in Co-Delivery Systems
The concept of the co-delivery approach first occurred from merging two research fields: drug delivery and gene therapy. Co-delivery systems combine at least two therapeutic agents with different physiological and physicochemical properties; thus, achieving clinical combination chemotherapy. Taking into consideration the co-delivery strategy, combination therapy via nanotechnology approaches has progressively become a desirable technique and one of the leading frontiers in research to find an efficient drug delivery system (DDS).
  • 1.6K
  • 29 Aug 2022
Topic Review
The Fra-1/AP-1 Oncoprotein
Among components of the AP-1 complex, the FOS-family transcription factor Fra-1, encoded by FOSL1, has emerged as a prominent therapeutic target. Fra-1 is overexpressed in most solid tumors, in response to the BRAF-MAPK, Wnt-beta-catenin, Hippo-YAP, IL-6-Stat3, and other major oncogenic pathways. In vitro functional analyses, validated in onco-mouse models and corroborated by prognostic correlations, show that Fra-1-containing dimers control tumor growth and disease progression. Fra-1 participates in key mechanisms of cancer cell invasion, Epithelial-to-Mesenchymal Transition, and metastatic spreading, by driving the expression of EMT-inducing transcription factors, cytokines, and microRNAs.
  • 1.6K
  • 06 May 2023
Topic Review
DNA Methylation in Cancer
DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation is strongly implicated in cancer development. Cancers possess an extensively hypomethylated genome with focal regions of hypermethylation at CPG islands. Due to the highly conserved nature of cancer-specific methylation, its detection in cell-free DNA in plasma using liquid biopsies constitutes an area of interest in biomarker research. The advent of next-generation sequencing and newer computational technologies have allowed for the development of diagnostic and prognostic biomarkers that utilize methylation profiling to diagnose disease and stratify risk. Methylome-based predictive biomarkers can determine the response to anti-cancer therapy. An additional emerging application of these biomarkers is in minimal residual disease monitoring. Several key challenges need to be addressed before cfDNA-based methylation biomarkers become fully integrated into practice. The first relates to the biology and stability of cfDNA. The second concerns the clinical validity and generalizability of methylation-based assays, many of which are cancer type-specific. The third involves their practicability, which is a stumbling block for translating technologies from bench to clinic. 
  • 1.6K
  • 26 Jan 2024
Topic Review
L19-TNF
Tumor necrosis factor (TNF) is used as a pro-inflammatory payload to trigger haemorrhagic necrosis and boost anti-cancer immunity at the tumor site. There is  a depotentiated version of TNF (carrying the single point mutation I97A), which displayed reduced binding affinity to its cognate receptor tumor necrosis factor receptor 1 (TNFR-1) and lower biocidal activity. 
  • 1.6K
  • 29 Mar 2022
Topic Review
Oncolytic Virotherapy
Some non-pathogenic viruses that do not cause serious illness in humans can efficiently target and kill cancer cells and may be considered candidates for cancer treatment with virotherapy. However, many cancer cells are protected from viruses. An important goal of personalized cancer treatment is to identify viruses that can kill a certain type of cancer cells. To this end, researchers investigate expression patterns of cell entry receptors, which viruses use to bind to and enter host cells.
  • 1.6K
  • 22 Dec 2020
Topic Review
Oral Bacteria and OSCC
Oral squamous cell carcinoma (OSCC) is an invasive epithelial neoplasm that is influenced by various risk factors, with a low survival rate and an increasing death rate. In the past few years, with the verification of the close relationship between different types of cancers and the microbiome, research has focused on the compositional changes of oral bacteria and their role in OSCC. Generally, oral bacteria can participate in OSCC development by promoting cell proliferation and angiogenesis, influencing normal apoptosis, facilitating invasion and metastasis, and assisting cancer stem cells. The study findings on the association between oral bacteria and OSCC may provide new insight into methods for early diagnosis and treatment development. 
  • 1.6K
  • 02 Nov 2020
Topic Review
FGFR3-TACCs3 Fusions in Human Glioblastoma
Glioma are the most frequent malignant primary CNS tumors in adults, with an incidence of 5–6 per 100,000 per year, with glioblastoma (with 3.2 per 100,000 per year) being the largest subgroup. The current therapy for glioblastoma is resection followed by radiochemotherapy and their prognosis is always fatal.Oncogenic fusion genes emerged as successful targets in several malignancies, such as chronic myeloic leukemia or lung cancer. Fusion of the fibroblast growth receptor 3 and the transforming acidic coiled coil containing protein – FGFR3-TACC3-fusion is prevalent in 3-4% of human glioblastoma. The fusion protein leads to constitutively activated kinase signaling of FGFR3 and thereby promotes cell proliferation and tumour progression. An overview on clinical and histomolecular features of FGFR3-TACC3-fusion positive glioblastoma is described and the cellular fuction of the fusion protein in glioblastoma cells is highlighted.
  • 1.6K
  • 24 Aug 2022
Topic Review
Neutrophil
Neutrophils represent about 50–70% of all white blood cells in the human circulation and are widely recognized as the first line of defense in infectious disease. However, neutrophils also have a clear modulatory role in human diseases such as cancer, respiratory disease, and autoimmunity. Infections and/or any inflammatory signals trigger a rapid influx of neutrophils from the peripheral blood to the inflammatory site, where they can utilize a broad variety of effector functions to.  Neutrophils are well known phagocytic cells, engulfing microorganisms or in case of bigger targets, such as cancer cells, taking “bites” of the membrane in a process called ‘trogocytosis’. Moreover, neutrophils are armed with granules that are loaded with proteases and inflammatory mediators  that are released upon activation. In addition, during a so called ‘oxidative burst’ neutrophils release high levels of  reactive oxygen species (ROS), which can trigger cell death of the target cell. Finally, neutrophils can entrap foreign materials in so called ‘neutrophil extracellular traps’ (NETs), which are mainly composed of neutrophil DNA and Granular contents. The effector functions of neutrophils can be triggered by antibodies that activate  neutrophils by binding to Fc-receptors (FcRs), leading to antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Although neutrophils are mainly involved in innate immunity, neutrophils contribute to adaptive immune responses. 
  • 1.6K
  • 05 Jan 2021
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