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Topic Review
Perhexiline
Perhexiline is a prophylactic antianginal drug known to act by inhibiting carnitine palmitoyltransferase 1 (CPT1) and 2 (CPT2), mitochondrial enzymes critical for fatty acid metabolism.
  • 1.0K
  • 05 May 2023
Topic Review
Lipids in Immunity to Cancer
While immunotherapies for diverse types of cancer are effective in many cases, relapse is still a lingering problem. Like tumor cells, activated immune cells have an anabolic metabolic profile, relying on glycolysis and the increased uptake and synthesis of fatty acids. In contrast, immature antigen-presenting cells, as well as anergic and exhausted T-cells have a catabolic metabolic profile that uses oxidative phosphorylation to provide energy for cellular processes. One goal for enhancing current immunotherapies is to identify metabolic pathways supporting the immune response to tumor antigens. A robust cell expansion and an active modulation via immune checkpoints and cytokine release are required for effective immunity. Lipids, as one of the main components of the cell membrane, are the key regulators of cell signaling and proliferation. Therefore, lipid metabolism reprogramming may impact proliferation and generate dysfunctional immune cells promoting tumor growth. Based on lipid-driven signatures, the discrimination between responsiveness and tolerance to tumor cells will support the development of accurate biomarkers and the identification of potential therapeutic targets. These findings may improve existing immunotherapies and ultimately prevent immune escape in patients for whom existing treatments have failed
  • 1.0K
  • 04 Nov 2020
Topic Review
Hilar Biliary Obstruction
Malignant hilar biliary obstruction (HBO) represents a complex clinical condition in terms of diagnosis, surgical and medical treatment, endoscopic approach, and palliation. The main etiology of malignant HBO is hilar cholangiocarcinoma that is considered an aggressive biliary tract’s cancer and has still today a poor prognosis.
  • 1.0K
  • 18 Mar 2021
Topic Review
Intertumoural and Intratumoural Heterogeneity in Melanoma
Tumour heterogeneity is a phenomenon where the cancer cells evolve diversely over the course of the disease. As a result of the evolution, the cancer cells can be found to be genetically, epigenetically and/or phenotypically different in order to survive in the human body. The tumour microenvironment also plays a crucial role during the evolution.
  • 1.0K
  • 01 Jul 2022
Topic Review
HLA-I and Cancer Derived Extracellular Vesicles
The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign cancer-related antigenic peptides has recently been highlighted by the successful application of monoclonal antibody-based checkpoint inhibitors as novel immune therapies. Thus, there is an increased interest in fully characterising the repertoire of peptides that are being presented to cytotoxic CD8+ T cells by cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all cancer cells. Whilst the peptide ligandome presented by cell surface HLA class I molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined.
  • 1.0K
  • 13 Jan 2022
Topic Review
Cancer Metastasis
Despite great advances in the detailed profiling of tumor cells and the development of therapeutic agents, cancer metastasis is still a big hurdle in the treatment of cancer patients. This is possibly because tumor cells plastically evolve through interplay with the host environment, including stromal cells, vascular cells, and immune cells. The reciprocal evolution among the numerous components further increases the heterogeneity and complexity in both tumor cells and the host, leading to refractory cancer. It is important to better understand the entire metastatic cascade and the practical implementations targeting the oncoimmune drivers in the mechanisms.
  • 1.0K
  • 24 Feb 2021
Topic Review
Thyroid Cancer Stem-Like Cells
Thyroid cancer (TC) is the most common endocrine malignancy. Recent progress in thyroid cancer biology revealed a certain degree of intratumoral heterogeneity, highlighting the coexistence of cellular subpopulations with distinct proliferative capacities and differentiation abilities. Among those subpopulations, cancer stem-like cells (CSCs) are hypothesized to drive TC heterogeneity, contributing to its metastatic potential and therapy resistance. CSCs principally exist in tumor areas with specific microenvironmental conditions, the so-called stem cell niches. In particular, in thyroid cancer, CSCs’ survival is enhanced in the hypoxic niche, the immune niche, and some areas with specific extracellular matrix composition.
  • 1.0K
  • 23 Jun 2021
Topic Review
Macrophages Proliferation in Health and Disease
Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. Macrophages comprise a heterogeneous and functionally versatile population of innate immune cells. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating TAMs self-renewal capacity may help to identify promising targets for the development of novel anticancer agents.
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  • 02 Nov 2022
Topic Review
Liver Transplantation for Perihilar Cholangiocarcinoma
Cholangiocarcinoma (CCA) encompasses all malignant neoplasms arising from the epithelial cells of the biliary tree. About 40% of CCAs are perihilar, involving the bile ducts distal to the second-order biliary branches and proximal to the cystic duct implant. About two-thirds of pCCAs are considered unresectable at the time of diagnosis or exploration. When resective surgery is deemed unfeasible, liver transplantation (LT) could be an effective alternative. The overall survival rates after LT at 1 and 3 years are 91% and 81%, respectively. The overall five-year survival rate after transplantation is 73% (79% for patients with underlying PSC and 63% for de novo pCCA). Multicenter case series reported a 5-year disease-free survival rate of ~65%.
  • 1.0K
  • 30 May 2023
Topic Review
Virotherapy against Glioblastoma
Recent advances in understanding of cancer biology have stimulated the development of numerous therapeutic approaches, one of which is virotherapy. Therapy by oncolytic viruses is a promising method for malignant tumors of various histogenesis, both as a monotherapy and as a part of combination therapy.
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  • 20 Feb 2024
Topic Review
Modeling Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are revolutionizing the treatment of cancer, but models that accurately predict their efficacy before administering them to humans are badly needed.  This entry presents the application of a microfluidic tumor model that simulates the interactions between immune cells and tumors in a dynamic microenvironment, utilizing real-time imaging and image analytic algorithms to demonstrate excellent correlations between the laboratory model and animal studies.  Future applications of the system in precision medicine will explore the use of the device for selecting patient-specific therapies for cancer.
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  • 26 Oct 2020
Topic Review
Clinical Applications of Short Non-Coding RNA-Based Therapies
RNA therapies have demonstrated clinical potential for both the treatment of cancer and other pathologies. Therapeutic delivery and resulting adverse events remain significant roadblocks in implementing many of these drugs into clinical practice, but the FDA approval of three Alnylam Pharmaceuticals’ small interfering RNAs (siRNAs) therapies has been a milestone in developing therapies tailored to disease-driving target genes. While it seems that RNAs can be administered “naked” in closed-compartment organs such as eyes and lungs, more research is needed for systemic administration. Lipid nanoparticles represent a promising delivery method, but some challenges remain because of their potential to elicit an immune response, relatively low circulation times, and relatively large size. The use of GalNAc for the delivery and targeting of siRNAs has made significant progress, but delivery systems targeted to organs other than the liver would broaden the range of diseases that could be treated with RNA therapies.
  • 1.0K
  • 07 Apr 2022
Topic Review
Oncolytic Virus Therapy for PDAC
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. 
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  • 22 Apr 2021
Topic Review
Metformin for Lung Cancer
Metformin is an oral biguanide which has been first-line treatment for type 2 diabetes for several years, however, research has showed that patients undergoing treatment with metformin have a decreased risk for cancer. Interestingly, the compund exhibits a considerable number of antitumor effects which could potentially improve lung cancer treatment. Nonetheless, data regarding the use of metformin as part of the therapeutic scheme for patients with lung cancer has been inconsistent to date. One of the points that the current literature fails to address is the differential effects of metformin in lean vs. obese subjects, which is well established in its use for diabetes, as well as its newly described mechanism of action which depends on redox status of the tumor cell.
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  • 04 Jul 2022
Topic Review
LncRNAs HOTAIR in BC therapy
Breast cancer (BC) is the most common cancer type among women, and morbidity and mortality rates are still very high. Despite new innovative therapeutic approaches for all BC molecular subtypes, the discovery of new molecular biomarkers involved in tumor progression has been fundamental for the implementation of personalized treatment strategies and improvement of patient management. Many experimental studies indicate that long non-coding RNAs (lncRNAs) are strongly involved in BC initiation, metastatic progression, and drug resistance. In particular, aberrant expression of HOX transcript antisense intergenic RNA (HOTAIR) lncRNA plays an important role in BC contributing to its progression and represents a predictor of BC metastasis. For its proven prognostic value, HOTAIR could represent a potential therapeutic target in BC.
  • 1.0K
  • 22 Oct 2020
Topic Review
Immunoproteasome
Proteasome inhibition is a promising strategy for the treatment of multiple myeloma; unfortunately, this disease is often associated with an increasing chemoresistance. One novel approach may be to target the immunoproteasome, a proteasomal isoform mainly present in cells of hematopoietic origin. We investigated the activity of a panel of amides against immunoproteasome core particles as potential agents for the treatment of multiple myeloma (MM). Amide 6 showed an ideal profile since it was able to inhibit both the chymotrypsin-like activities of the immunoproteasome with Ki values of 4.90 µM and 4.39 µM for β1i and β5i, respectively, coupled with an EC50 =17.8 µM against MM.1R cells. Compound 6 inhibited also ubiquitinated protein degradation and was able to act on different phases of MM cell cycle reducing the levels of cyclin A/CDK1, cyclin B/CDK1 and cyclin D/CDK4/6 complexes, which turns in cell cycle arrest.
  • 1.0K
  • 03 Nov 2020
Topic Review
Strategies Directly Targeting Mutated KRAS
KRAS gene mutation is widespread in tumors and plays an important role in various malignancies. Targeting KRAS mutations is regarded as the “holy grail” of targeted cancer therapies. Multiple strategies, including covalent binding strategy, targeted protein degradation strategy, targeting protein and protein interaction strategy, salt bridge strategy, and multivalent strategy, have been adopted to develop KRAS direct inhibitors for anti-cancer therapy. Various KRAS-directed inhibitors have been developed, including the FDA-approved drugs sotorasib and adagrasib, KRAS-G12D inhibitor MRTX1133, and KRAS-G12V inhibitor JAB-23000, etc. The different strategies greatly promote the development of KRAS inhibitors. 
  • 1.0K
  • 27 Apr 2023
Topic Review
Translational Formulation Technologies for Cancer-Therapy
Over the past few decades, the field of cancer therapy has seen a significant change in the way in which formulations are designed and developed, resulting in more efficient products that allow us to ultimately achieve improved drug bioavailability, efficacy, and safety. However, although many formulations have entered the market, many others have fallen by the wayside leaving the scientific community with several lessons to learn.
  • 1.0K
  • 16 Nov 2020
Topic Review
Hypoxia
Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. These events favor tumor progression and chemoresistance. The increase in glucose and amino acid uptake, glycolytic flux, and lactate production; the alterations in glutamine metabolism, tricarboxylic acid cycle, and oxidative phosphorylation; the high levels of mitochondrial reactive oxygen species; the modulation of both fatty acid synthesis and oxidation are hallmarks of the metabolic rewiring induced by hypoxia.
  • 1.0K
  • 18 Dec 2020
Topic Review
Eckols: Potential Cancer Therapies
In recent years, an increased interest in marine macroalgae bioactive compounds has been recorded due to their benefits to human health and welfare. Several of their bioactivities have been demonstrated, such as anti-inflammatory, antioxidant, anticarcinogenic, antibacterial and antiviral behavior.However, there is still lacking a clear definition to how these compounds exert their bioactive properties. Of all bioactive compounds from marine macroalgae, attention has been focused on phenolic compounds, specifically in phlorotannins, due to their potential for biomedical applications. Phlorotannins are a diverse and wide group of phenolic compounds, with several structural variations with base in the monomer phloroglucinol. Of all the diverse phlorotannins structures, eckol-family of phlorotannins demonstrates remarkable bioactivity, especially regarding anti-tumoral properties.
  • 1.0K
  • 13 Jun 2022
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