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Topic Review
ACSL3 and ACSL4 in Ferroptosis
Ferroptosis involves cell metabolism, regulations of reactive oxygen species (ROS), and iron metabolism. To trigger ferroptosis, specific lipids must undergo peroxidation, and the natural defense mechanisms that prevent the accumulation of peroxidized lipids must be compromised. Acyl CoA synthetase (ACSLs) play an important role in tissue cell metabolism, and different isoforms have different tissue distributions and substrate preferences, which regulate different intracellular lipid compositions. Among these five isoforms, ACSL3 and ACSL4 have been shown to participate in ferroptosis. In addition, ACSL4 is a positive regulator in ferroptosis, whereas ACSL3 contributes to cancer cells acquiring ferroptosis resistance.
  • 819
  • 15 Dec 2022
Topic Review
Cholic Acid
Matrix metalloproteinase-9 (MMP-9) plays a crucial role in cell invasion and cancer metastasis. In this study, we showed that cholic acid (CA), a major primary bile acid, can induce MMP-9 expression in colon cancer HT29 and SW620 cells. CA increased reactive oxygen species (ROS) production and also activated phosphorylation of ERK1/2, JNK, and p38 MAPK. Specific inhibitors and mutagenesis studies showed that ERK1/2 and JNK functioned as upstream signals in the activation of AP-1, and p38 MAPK functioned as an upstream signal in the activation of NF-κB. N-acetyl-L-cysteine (NAC, an ROS scavenger) and diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor) inhibited CA-induced activation of ERK1/2, JNK, and p38 MAPK, indicating that ROS production by NADPH oxidase could be the furthest upstream signal in MMP-9 expression. Colon cancer cells pretreated with CA showed remarkably enhanced invasiveness. Such enhancement was partially abrogated by MMP-9-neutralizing antibodies. These results demonstrate that CA could induce MMP-9 expression via ROS-dependent ERK1/2, JNK-activated AP-1, and p38-MAPK-activated NF-κB signaling pathways, which in turn stimulate cell invasion in human colon cancer cells.
  • 818
  • 30 Oct 2020
Topic Review
Therapies for Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is the fourth leading cause of cancer-related mortality worldwide, with a five-year survival rate of less than 8%. It can be classed into endocrine and exocrine tumours with PDAC, a form of exocrine pancreatic cancer, the most common form. The high mortality rate associated with PDAC is primarily due to delayed diagnosis and tumour resistance to chemotherapy. A broad range of non-specific symptoms are associated with PDAC such as abdominal pain, jaundice, dry/itchy skin, steatorrhoea, and bilirubinuria. Surgery is the primary treatment option, with chemotherapy being administered as adjuvant therapy in select cases.  Resistance to chemotherapy has become a critical problem in the treatment of PDAC, with most patients displaying resistance patterns. 
  • 818
  • 02 Sep 2022
Topic Review
Signaling Lymphocytic Activation Molecule Family
The signaling lymphocytic activation molecule (SLAM) family receptors are expressed on various immune cells and malignant plasma cells in multiple myeloma (MM) patients. In immune cells, most SLAM family molecules bind to themselves to transmit co-stimulatory signals through the recruiting adaptor proteins SLAM-associated protein (SAP) or Ewing’s sarcoma-associated transcript 2 (EAT-2), which target immunoreceptor tyrosine-based switch motifs in the cytoplasmic regions of the receptors. Notably, SLAMF2, SLAMF3, SLAMF6, and SLAMF7 are strongly and constitutively expressed on MM cells that do not express the adaptor proteins SAP and EAT-2.
  • 817
  • 26 Jan 2021
Topic Review
Amino Acids in Cancer
Cancer metabolism is an emerging field of investigation aimed at identifying cancer cell vulnerabilities in order to define novel anti-cancer therapeutic approaches based on interventions that modulate the availability of specific nutrients. Amino acids (AAs) are used by cancer cells as both building blocks for protein synthesis required for rapid tumor growth and as sources of energy. 
  • 817
  • 06 Dec 2022
Topic Review
Non-Coding RNA in Melanoma
Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules (ncRNAs) in the fine tuning of melanoma progression. Studies have shown that ncRNAs, among them microRNAs and lncRNAs, play a role in melanoma invasion, metastasis and acquired resistance to treatment. In addition, they could serve as prognostic/diagnostic biomarkers and potential targets for promising therapeutic strategies. 
  • 815
  • 26 Nov 2020
Topic Review
Treatment Strategies for Glioblastoma Multiforme
Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM. Oncolytic viral therapy and other immunogenic cell death-inducing treatments bridge the antitumor strategy with immunization and installation of immune control over the disease. These strategies should be included in the standard treatment protocol for GBM. Some immunotherapies are individualized in terms of the medicinal product, the immune target, and the immune tumor–host contact. Current individualized immunotherapy strategies focus on combinations of approaches. Standardization appears to be impossible in the face of complex controlled trial designs.
  • 815
  • 24 Jan 2021
Topic Review
Carbonic Anhydrase IX Inhibitors and Solid Tumors
Carbonic anhydrase (CA, EC 4.2.1.1) IX isoform is a surficial zinc metalloenzyme that is proven to play a central role in regulating intra and extracellular pH, as well as modulating invasion and metastasis processes. With its strong association and distribution in various tumor tissues and well-known druggability, this protein holds great promise as a target to pharmacologically interfere with the tumor microenvironment by using drug combination regimens.
  • 815
  • 20 Apr 2022
Topic Review
Exosomes and Extracellular Vesicles
Exosomes are endosome-derived nanovesicles produced by healthy as well as diseased cells. Their proteic, lipidic and nucleic acid composition is related to the cell of origin, and by vehiculating bioactive molecules they are involved in cell-to-cell signaling, both in healthy and pathologic conditions. Being nano-sized, non-toxic, biocompatible, scarcely immunogenic, and possessing targeting ability and organotropism, exosomes have been proposed as nanocarriers for their potential application in diagnosis and therapy. Among the different techniques exploited for exosome isolation, the sequential ultracentrifugation/ultrafiltration method seems to be the gold standard; alternatively, commercially available kits for exosome selective precipitation from cell culture media are frequently employed. To load a drug or a detectable agent into exosomes, endogenous or exogenous loading approaches have been developed, while surface engineering procedures, such as click chemistry, hydrophobic insertion and exosome display technology, allow for obtaining actively targeted exosomes. 
  • 814
  • 23 Jan 2021
Topic Review
Isoliquiritigenin in Cancer
Isoliquiritigenin (ISL), a natural bioactive compound with a chalcone structure, demonstrates high antitumor efficacy. 
  • 813
  • 08 Feb 2021
Topic Review
Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma (cSCC) is a common type of neoplasia, representing a terrible burden on patients’ life and clinical management. Although it seldom metastasizes, and most cases can be effectively treated with surgical intervention, once metastatic, cSCC displays considerable aggressiveness leading to the death of affected individuals. No consensus has been reached as to which features better characterize the aggressive behavior of cSCC, an achievement hindered by the high mutational burden caused by chronic ultraviolet light exposure. Even though some subtypes have been recognized as high risk variants, depending on certain tumor features, cSCC that are normally thought of as low risk could pose increased danger to the patients. In light of this, specific genetic and epigenetic markers for cutaneous SCC, which could serve as reliable diagnostic markers and possible targets for novel treatment development, are currently searched for. 
  • 811
  • 25 Jul 2020
Topic Review
Fasting, Hormones, and Cancer Prevention
Hormonal and growth factor alterations, related to an elevated food consumption and excessive adiposity, affect the regulation of genes involved in cellular processes including proliferation, differentiation and DNA repair, allowing cells to survive and proliferate despite the accumulation of mutations which lead to malignant transformation. The growth hormone/insulin growth factor-1 (GH/IGF-1)/ insulin pathway and its downstream effectors, in fact, are known to promote aging and/or age-related diseases, including cancer, in many model organisms. The restriction of nutrients is established to have strong effects on levels of hormones and growth factors, delaying the incidence of age-related diseases and prolonging lifespan.
  • 811
  • 28 Oct 2021
Topic Review
Treatment of irAE Colitis
Immune checkpoint inhibitor treatment has shown revolutionary therapeutic effects in various carcinomas. However, immune-related adverse events (irAE) following the treatment can sometimes lead to treatment discontinuation. One such frequently encountered adverse event is immune-related colitis (irAE colitis). Corticosteroids (CS) are the first-line treatment for irAE colitis, but we often encounter CS-refractory or resistant cases. Application of multiple biologics has been proposed as a therapeutic drug to be administered after CS treatment; however, the efficacy and safety of biologics for patients with irAE colitis who do not respond to CS have not been established. The treatment regimens available for irAE colitis is summarized, focusing on the mechanism of action of corticosteroids, infliximab, vedolizumab, and other drugs.
  • 810
  • 22 Jun 2022
Topic Review
177Lu-PSMA Therapy
177Lu-PSMA (prostate specific membrane antigen) therapy is used for metastatic castration-resistant prostate cancer (mCRPC). Although there are some different approaches regarding the use of 177Lu-PSMA therapy in different countries, this type of therapy is generally safe, with a low toxicity profile. From the oncological point of view, a PSA (prostate specific antigen) decline of ≥50% was seen in 10.6–69% of patients with mCRPC; whereas progression-free survival (PFS) was reported to be 3–13.7 months in different studies. Consequently, 177Lu-PSMA therapy is a promising treatment in patients with mCRPC, with good clinical efficacy, even in heavily pretreated patients with multiple lines of systemic therapy. Currently, there are ongoing clinical trials in the United States, including a phase III multicenter FDA registration trial. 
  • 807
  • 23 Jun 2021
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. 
  • 807
  • 22 Jun 2022
Topic Review
JAK inhibitors and immune system
The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is aberrantly activated in many malignancies. Inhibition of this pathway via JAK inhibitors (JAKinibs) is therefore an attractive therapeutic strategy underlined by Ruxolitinib (JAK1/2 inhibitor) being approved for the treatment of myeloproliferative neoplasms. As a consequence of the crucial role of the JAK-STAT pathway in the regulation of immune responses, inhibition of JAKs suppresses the immune system. This review article provides a thorough overview of the current knowledge on JAKinibs’ effects on immune cells in the context of hematological malignancies. We also discuss the potential use of JAKinibs for the treatment of diseases in which lymphocytes are the source of the malignancy.
  • 806
  • 23 Jun 2021
Topic Review
D-2-Hydroxyglutarate in Glioma Biology
Oncometabolites, the abnormally accumulated metabolites derived from disrupted cancer metabolic pathways, are a recently defined concept in cancer biology. Isocitrate dehydrogenase (IDH) mutations are common genetic abnormalities in glioma, which result in the accumulation of an “oncometabolite”, D-2-hydroxyglutarate (D-2-HG). Abnormally elevated D-2-HG levels result in a distinctive pattern in cancer biology, through competitively inhibiting α-ketoglutarate (α-KG)/Fe(II)-dependent dioxgenases (α-KGDDs). D-2-HG affects DNA/histone methylation, hypoxia signaling, DNA repair, and redox homeostasis, which impacts the oncogenesis of IDH-mutated cancers.
  • 805
  • 08 Oct 2021
Topic Review
Adrenocortical Carcinoma pathological features
Adrenocortical carcinoma (ACC) is a heterogenous group of diseases with different clinical be-haviour between adult and paediatric patients. In addition, three histological variants, oncocytic, myxoid and sarcomatoid are noted on the recent World Health Organisation (WHO) classification of ACC. A review of recent literature showed that the different types of ACC have distinctive demographic data, clinical presentation, pathology, biological behaviour, genomic and patients’ prognosis. In addition, recent updates of pathology staging for ACC allow refinement of prognos-tic grouping for planning treatment of the patients with ACC.
  • 804
  • 28 Sep 2021
Topic Review
Flavonoids Synergistically Enhance Anti-Glioblastoma Effects of Chemotherapeutic Drugs
Flavonoids are polyphenolic plant secondary metabolites with pleiotropic biological properties, including anti-cancer activities. These natural compounds have potential utility in glioblastoma (GBM), a malignant central nervous system tumor derived from astrocytes. 
  • 803
  • 16 Dec 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.
  • 803
  • 14 Dec 2022
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