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Topic Review
MicroRNAs in Ovarian Cancer Metastasis
Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and the major cause of death is attributed to metastasis. EOC metastasizes mainly through the transcoelomic pathway, in which cells disseminate from the primary EOC tumor by undergoing epithelial-to-mesenchymal transition (EMT), float freely as spheroids in the ascitic fluid, and then attach onto the mesothelium lining or invade deeper into the peritoneal organs. In addition, metastatic EOC cells can transit in the blood or lymph vessels and undergo extravasation to establish new tumors in hematogenous and lymphatic metastasis. MicroRNAs (miRNAs) are a group of small non-coding RNAs that exert important regulatory functions in many biological processes through their effects on regulating gene expression.  Numerous studies have reported that miRNAs can suppress or promote EOC metastasis by regulating the expression of genes involved in various events related to metastasis, such as EMT, cell migration and invasion, as well as tumor angiogenesis and immune suppression. 
  • 1.0K
  • 14 Oct 2020
Topic Review
PFKFB3 and PFKFB4 in Cancer
Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. 
  • 1.0K
  • 11 Mar 2021
Topic Review
Microbiota-Derived Short-Chain Fatty Acids in Colorectal Cancer Therapy
Microbiota-derived short-chain fatty acids (SCFAs), namely acetate, butyrate, and propionate, have the ability to modulate the tumor microenvironment in distinct ways. SCFAs promote immune cell differentiation, downregulate the expression of pro-inflammatory mediators, and restrict the tumor-induced angiogenesis. SCFAs also sustain the integrity of basement membranes and modulate the intestinal pH. Colorectal cancer (CRC) patients have lower concentrations of SCFAs than healthy individuals. Increasing the production of SCFAs through the manipulation of the gut microbiota could constitute an important therapeutic strategy towards CRC due to their antitumorigenic effect and ability of modulating tumor microenvironment.
  • 1.0K
  • 23 Apr 2023
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. 
  • 1.0K
  • 19 Apr 2021
Topic Review
Metabolism-Associated Epigenetic and Immunoepigenetic Re-programming in Liver Cancer
Metabolic reprogramming and epigenetic changes have been characterized as hallmarks of liver cancer. Metabolic intermediates serve as crucial substrates for various epigenetic modulations, from post-translational modification of histones to DNA methylation. In turn, epigenetic changes can alter the expression of metabolic genes supporting on the one hand, the increased energetic demand of cancer cells and, on the other hand, influence the activity of tumor-associated immune cell populations. In this review, we will illustrate the most recent findings about metabolic reprogramming in liver cancer. We will focus on the metabolic changes characterizing the tumor microenvironment and on how these alterations impact on epigenetic mechanisms involved in the malignant progression. Furthermore, we will report our current knowledge about the influence of cancer-specific metabolites on epigenetic reprogramming of immune cells. Finally, we will review the current strategies to target metabolic and epigenetic pathways and their therapeutic potential in liver cancer, alone or in combinatorial approaches.
  • 1.0K
  • 13 Dec 2021
Topic Review
Epigenetic Alterations in Salivary Gland Tumors
Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation of SGCs. Epigenetic modifications are any heritable changes in gene expression that are not caused by changes in DNA sequence. It is widely accepted that epigenetics plays an important role in SGC development.
  • 1.0K
  • 16 Jun 2023
Topic Review
Neoadjuvant treatment in breast cancer
Neoadjuvant Chemotherapy (NAC) in Breast Cancer (BC) has proved useful for the reduction in tumor burden prior to surgery, allowing for a more extensive breast preservation and the eradication of subjacent micrometastases. However, the impact on prognosis is highly dependent on the establishment of Pathological Complete Response (pCR), in particular for Triple Negative (TN) and Hormonal Receptor negative/Human Epidermal growth factor Receptor 2 positive (HR−/HER2+) subtypes. Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. Major evolution events during BC NAC that feature the Residual Disease (RD) are the loss of HR and HER2, which are prognostic of bad outcome, and stemness and immune depletion-related gene expression aberrations. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease.breast cancer; neoadjuvant chemotherapy; pathological complete response; predictive markers; residual diseasebreast cancer; neoadjuvant chemotherapy; pathological complete response; predictive markers; residual disease
  • 999
  • 08 Aug 2020
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.
  • 999
  • 03 Dec 2021
Topic Review
Epigenetics in Myeloid Diseases
Mutations in genes encoding chromatin regulators are early events contributing to developing asymptomatic clonal hematopoiesis of indeterminate potential and its frequent progression to myeloid diseases with increasing severity. We focus on the subset of myeloid diseases encompassing myelodysplastic syndromes and their transformation to secondary acute myeloid leukemia. We introduce the major concepts of chromatin regulation that provide the basis of epigenetic regulation. In greater detail, we discuss those chromatin regulators that are frequently mutated in myelodysplastic syndromes. We discuss their role in the epigenetic regulation of normal hematopoiesis and the consequence of their mutation. Finally, we provide an update on the drugs interfering with chromatin regulation approved or in development for myelodysplastic syndromes and acute myeloid leukemia.
  • 998
  • 20 Apr 2021
Topic Review
TGF-β and ROS in Cancer
Metabolic changes in tumor microenvironment play a critical role in cancer, related to the accumulated alterations in signaling pathways that control cellular metabolism. Cancer metabolic deregulation is related to specific events such as the control of oxidative stress, and in particular the redox imbalance with aberrant oxidant production and/or a deregulation of the efficacy of the antioxidant systems. In cancer cells, different cytokines are involved in the development and/or progression of cancer: among these cytokines, the transforming growth factor β (TGF-β) is central to tumorigenesis and cancer progression. In tumor cells, it has been demonstrated that there is a close correlation between oxidative stress and TGF-β: this crosstalk strongly contributes to tumorigenesis, both in tumor development and in mediating its invasiveness.
  • 998
  • 09 Jul 2021
Topic Review
GPR56 a Novel Immune Checkpoint on Tumor-Infiltrating Lymphocytes
Despite the clinical efficacy of so-called immune checkpoint inhibitors (ICIs) in various cancers, some cancer types, including epithelial ovarian cancer (EOC), do not effectively respond to current therapeutics. Thus, the identification of new immune checkpoints that regulate T cell immunity remains of great interest. One as yet largely uninvestigated checkpoint of potential interest is the G protein-coupled receptor 56 (GPR56), which belongs to the adhesion GPCR family. Here in this study,   it was identified that GPR56 is expressed on tumor infiltrating lymphocytes (TILs) and investigated its role as a potential immune checkpoint within the context of cancer. Based on the investigated data, GPR56 indeed appears to function as an immune checkpoint in TILs and may thus provide a novel immunotherapeutic target for the reactivation of tumor-infiltrating and tumor-reactive lymphocytes.
  • 998
  • 22 Nov 2022
Topic Review
Role of p53 and TAp73 in Neuroblastoma
Neuroblastoma is the most common extracranial pediatric tumor. Although children with low- and intermediate-risk neuroblastoma, which correspond to approximately half of all newly diagnosed cases, have a good event-free and overall survival, high-risk neuroblastoma can be extremely aggressive and hard-to-treat tumors. In neuroblastoma, p53 and TAp73 act as safeguards against malignant transformation, but they are commonly inhibited by negative regulators, such as MDMs, Itch, and Aurora kinase A.
  • 998
  • 18 Jan 2023
Topic Review
Ovarian clear cell carcinoma (CCC)
Ovarian clear cell carcinoma (CCC) exhibits unique characteristics, including slow growth, glycogen accumulation in the cytoplasm, and poor prognosis for stress resistance. Several molecular targeting agents have failed to treat ovarian CCC. Recent reports have identified metabolic alterations through HNF1B, which is highly expressed in ovarian CCC. The Warburg effect, GSH synthesis, and mitochondrial regulation occur in CCC. The metabolic behaviors of ovarian CCC resemble the evolution of life to survive in stressful environments. Understanding the fundamental biology of ovarian CCC might help in the development of novel therapeutic strategies. 
  • 997
  • 08 Jun 2021
Topic Review
DNA-Dependent Protein Kinase Catalytic Subunit
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key component of the DNA-PK complex that has a well-characterized function in the non-homologous end-joining repair of DNA double-strand breaks. Since its identification, a large body of evidence has demonstrated that DNA-PKcs is frequently overexpressed in cancer, plays a critical role in tumor development and progression, and is associated with poor prognosis of cancer patients.
  • 997
  • 23 Jan 2021
Topic Review
Tumor Immune Microenvironment in MPM
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13–15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients’ genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.
  • 996
  • 23 Jun 2021
Topic Review
Natural/Designed Toxins for Precise Therapy
Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies.   
  • 996
  • 28 Jun 2021
Topic Review
Breast Cancer-Associated Fibroblasts
Breast cancer-associated fibroblasts (BCAFs) are the CAFs present in breast cancers with genetic and phenotypic characteristics similar to CAFs. CAFs originate from a diverse range of cells, including endothelial cells, adipocytes, pericytes, and MSCs. Although CAFs were derived from endothelial cells and pericytes, the derivation was not tested in breast cancer models similar to other cancers. BCAFs have also been derived from adipocytes that lead to a desmoplastic microenvironment. BCAFs can originate from MSCs, which contribute to angiogenesis through up-regulation of clusterin leading to tumorigenesis. BCAFs possess the fibrillar collagen receptor, DDR2, which rearranges collagen fibers to develop an invasive and metastatic TME. Additionally, integrin α11 in BCAFs interacts with platelet-derived growth factor receptor beta (PDGFRβ) and promotes invasiveness by activating c-Jun N-terminal kinase (JNK) and producing a matricellular protein, tenascin C.
  • 996
  • 14 Jan 2022
Topic Review
Biomarkers in Anal Cancer
Squamous cell carcinoma of the anal canal (SCCA) is a rare neoplasm, but with rising incidence rates in the past few decades; it is etiologically linked with the human papillomavirus (HPV) infection and is especially prevalent in immunocompromised patients, mainly those infected with HIV. 
  • 996
  • 30 Aug 2022
Topic Review
Tumor-Nerves Interactions
The interaction between neurons and a tumor are bilateral and promote metastasis on one hand, and the formation of new nerve structures (neoneurogenesis) on the other. Substances such as neurotransmitters and neurotrophins being the main actors in such interplay, it seems reasonable to expect that alternative splicing and the different populations of protein isoforms can affect tumor-derived neurogenesis. 
  • 995
  • 23 Jun 2021
Topic Review
Oncogene Driver Mutations and Therapeutic Implications in CRC
Genetic alterations in advanced colorectal cancer (CRC) have shown a negative predictive and prognostic role in specific target therapies. The assessment of RAS and BRAF genes and mismatch repair (MMR)/microsatellite status should be evaluated as molecular panel upfront in all cases of CRC to drive patients’ selection toward biological approved treatments.
  • 995
  • 08 Aug 2022
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