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Topic Review
DNA Polymerases
Recent studies on tumor genomes revealed that mutations in genes of replicative DNA polymerases cause a predisposition for cancer by increasing genome instability. The past 10 years have uncovered exciting details about the structure and function of replicative DNA polymerases and the replication fork organization. The principal idea of participation of different polymerases in specific transactions at the fork proposed by Morrison and coauthors 30 years ago and later named “division of labor,” remains standing, with an amendment of the broader role of polymerase δ in the replication of both the lagging and leading DNA strands. However, cancer-associated mutations predominantly affect the catalytic subunit of polymerase ε that participates in leading strand DNA synthesis. 
  • 1.7K
  • 14 Dec 2020
Topic Review
Vimentin at the Heart of Epithelial Mesenchymal Transition
Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. 
  • 1.7K
  • 22 Oct 2021
Topic Review
Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients
Neuroblastoma is the most common extracranial solid tumor of childhood, with a median age at diagnosis of 17 months. Its incidence is 10.2 cases per million children aged <15 years. Neuroblastoma arises in tissues of the sympathetic nervous system, mostly in the adrenal medulla or paraspinal ganglia. It appears as a mass in the abdomen, pelvis, neck, or chest, with about half of the patients having metastatic disease at diagnosis. The presence of metastatic diseases over the age of 12 or 18 months and aggressive biological features (e.g., MYCN oncogene amplification) define high-risk neuroblastoma. The prognosis for such patients is poor, with a long-term survival rate of only 40%.
  • 1.7K
  • 07 Jan 2022
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.
  • 1.7K
  • 18 Mar 2021
Topic Review
P53 DNA Binding Cooperativity Mutations
p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.
  • 1.7K
  • 23 Jun 2021
Topic Review
Cisplatin
Cisplatin, also referred to as cis-diamminedichloroplatinum (II) (CDDP), is a widely used, Pt-based anti-cancer chemotherapeutic agent. This transition metal coordination complex has a square planar molecular geometry and presents as a solid, yellow powder at room temperature. CDDP is fairly insoluble in most substances; however, it can be dissolved in dimethylformamide, and is somewhat soluble in water, but most preferable in saline sodium. In solid form, CDDP is stable for about two years if stored at room temperature in dry conditions and light protected; however, it is known to convert slowly to its trans-form. The stability of CDDP in sodium chloride solution is dependent on the chloride ion concentration; it is more stable when suspended in normal saline (0.9% sodium chloride). Saline also provides a reno-protective function, increasing hydration and aiding in excretion of CDDP from the kidneys.
  • 1.7K
  • 14 Dec 2022
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).
  • 1.7K
  • 25 Dec 2020
Topic Review
T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles
Extracellular vesicles (EV) are a very diverse group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular exchange, both nearby and systemically, since they induce signals and transmit their cargo (proteins, lipids, miRNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. However, cell surface receptor-induced EV release is limited to cells from the immune system, including T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptors for antigen and several bioactive molecules, including proapoptotic proteins. These EV are specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy.
  • 1.7K
  • 29 Mar 2022
Topic Review
Aurora Kinases in Lung Cancer
Lung cancer has remained one of the major causes of death worldwide. Thus, a more effective treatment approach is essential such as the inhibition of specific cancer-promoting molecules. Aurora kinases regulate the process of mitosis - a process of cell division that is necessary for normal cell proliferation. However, dysfunction of these kinases can contribute to cancer formation. The aberrant expression of Aurora kinases in lung cancer points to their crucial role in lung carcinogenesis. Therefore, understanding the fundamental functions as well as the cellular localization of Aurora kinases may contribute to evaluate their precise oncogenic function that will may lead to better specific targeting of these cancer-related molecules.  
  • 1.7K
  • 07 Jul 2021
Topic Review
Structure and Function of Sorting Nexin 27
SNX27 belongs to the sorting nexin (SNX) family of proteins that play a critical role in protein sorting and trafficking in the endocytosis pathway. This protein family is characterized by the presence of a Phox (PX) domain; however, SNX27 is unique in containing an additional PDZ (post-synaptic density 95/discs large/zonula occludens-1) domain.
  • 1.7K
  • 29 Jan 2023
Topic Review
Fisetin in Cancer
Fisetin is a flavonoid naturally occurring in various plants that possesses anticancer activity. It has the power to stop cancers from growing quickly, becoming invasive, and spreading to multiple tissues.
  • 1.7K
  • 10 May 2023
Topic Review
Glycosylation of Cancer Extracellular Vesicles
Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the tumor-associated glycans have already been identified in cancer EVs, which constitutes valuable sources of cancer biomarkers. Furthermore, glycans have also shown to play a role in EV protein sorting, uptake and tropism. Altogether, the EV glycan signatures hold tremendous potential to be applied into the clinical setting for both biomarker discovery and as therapeutic delivery systems.
  • 1.7K
  • 25 Jan 2021
Topic Review
Targeting Tumor-Associated Macrophages
Immune checkpoint inhibitors (ICIs) represent a promising therapeutic intervention for a variety of advanced/metastatic solid tumors, including melanoma, but in a large number of cases, patients fail to establish a sustained anti-tumor immunity and to achieve a long-lasting clinical benefit. Cells of the tumor micro-environment such as tumor-associated M2 macrophages (M2-TAMs) have been reported to limit the efficacy of immunotherapy, promoting tumor immune evasion and progression. 
  • 1.7K
  • 06 May 2021
Topic Review
Natural Blockers of PD-1/PD-L1 Interaction
The limited treatment options for triple-negative breast cancer with brain metastasis (TNBC-BM) have left the door of further drug development for these patients wide open. Although immunotherapy via monoclonal antibodies has shown some promising results in several cancers including TNBC, it cannot be considered the most effective treatment for brain metastasis. This is due to the protective role of the blood–brain barrier (BBB) which limits the entrance of most drugs, especially the bulky ones such as antibodies, to the brain. For a drug to traverse the BBB via passive diffusion, various physicochemical properties should be considered. 
  • 1.6K
  • 11 Jan 2023
Topic Review
PTEN in different TME compartments
Mounting preclinical and clinical evidence indicates that rewiring the host immune system in favor of an antitumor microenvironment achieves remarkable clinical efficacy in the treatment of many hematological and solid cancer patients. Nevertheless, despite the promising development of many new and interesting therapeutic strategies, many of these still fail from a clinical point of view, probably due to the lack of prognostic and predictive biomarkers. In that respect, several data shed new light on the role of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) in affecting the composition and function of the tumor microenvironment (TME) as well as resistance/sensitivity to immunotherapy. In this review, we summarize current knowledge on PTEN functions in different TME compartments (immune and stromal cells) and how they can modulate sensitivity/resistance to different immunological manipulations and ultimately influence clinical response to cancer immunotherapy
  • 1.6K
  • 04 Aug 2020
Topic Review
ACT Therapy for Solid Tumors
Adoptive cell therapy (ACT) with tumor-infiltrating T cells (TILs) has emerged as a promising therapy for the treatment of unresectable or metastatic solid tumors. One challenge to finding a universal anticancer treatment is the heterogeneity present between different tumors as a result of genetic instability associated with tumorigenesis. As the epitome of personalized medicine, TIL-ACT bypasses the issue of intertumoral heterogeneity by utilizing the patient’s existing antitumor immune response. Despite being one of the few therapies capable of inducing durable, complete tumor regression, many patients fail to respond. Recent research has focused on increasing therapeutic efficacy by refining various aspects of the TIL protocol, which includes the isolation, ex vivo expansion, and subsequent infusion of tumor specific lymphocytes.
  • 1.6K
  • 05 May 2021
Topic Review
Glioblastoma Organoids
Glioblastoma (GB) is the most lethal primary adult brain tumor. The great number of mutations involved and the aggressiveness of glioblastoma render this type of cancer especially difficult to investigate. Moreover, the lack of reliable GB models, together with its considerable clinical heterogeneity, has impaired a comprehensive investigation of the mechanisms that lead to tumorigenesis, cancer progression, and response to treatments. To address this problem, cerebral organoids have emerged as promising tools to investigate brain biology and to recapitulates the major steps involved in glioblastoma tumorigenesis. Here we exemplify relevant aspects of 3D models of glioblastoma, with a specific focus on organoids and their involvement in basic and translational research.
  • 1.6K
  • 25 Nov 2020
Topic Review
Lynch Syndrome (LS)
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). 
  • 1.6K
  • 22 Aug 2023
Topic Review
Esophageal and Gastric Tumors
Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is significant, with esophageal and gastric cancer representing the ninth and fifth most common cancers, respectively. The approach to diagnosis and staging of these lesions is multimodal and includes a combination of gastrointestinal endoscopy, endoscopic ultrasound, and cross-sectional imaging. Likewise, therapy is multidisciplinary and combines therapeutic endoscopy, surgery, radiotherapy, and systemic chemotherapeutic tools. Future directions for diagnosis of esophageal and gastric malignancies are evolving rapidly and will involve advances in endoscopic and endosonographic techniques including tethered capsules, optical coherence tomography, along with targeted cytologic and serological analyses. 
  • 1.6K
  • 23 Feb 2021
Topic Review
Extracellular matrix in tumor microenvironment
The tumor microenvironment (TME) has become the focus of interest in cancer research and treatment. It includes the extracellular matrix (ECM) and ECM-modifying enzymes that are secreted by cancer and neighboring cells. The ECM serves both to anchor the tumor cells embedded in it and as a means of communication between the various cellular and non-cellular components of the TME. The cells of the TME modify their surrounding cancer-characteristic ECM. This in turn provides feedback to them via cellular receptors, thereby regulating, together with cytokines and exosomes, differentiation processes as well as tumor progression and spread. Matrix remodeling is accomplished by altering the repertoire of ECM components and by biophysical changes in stiffness and tension caused by ECM-crosslinking and ECM-degrading enzymes, in particular matrix metalloproteinases (MMPs). These can degrade ECM barriers or, by partial proteolysis, release soluble ECM fragments called matrikines, which influence cells inside and outside the TME.
  • 1.6K
  • 19 Jan 2021
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