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Topic Review
Androgen Receptor in Lung Cancer
The androgen receptor (AR) is expressed in many cell types, and its related signaling is widely investigated in hormone-dependent cancers such as prostate and breast. The significance of the AR, however, has been detected even in other cancers, including gastric, bladder, kidney, lung, hepatic, and pancreatic, in which growth and spreading are not strictly or notoriously dependent on sex steroid hormone action. 
  • 1.2K
  • 15 Jun 2023
Topic Review
Oncogenic Tyrosine Phosphatases
Despite a large number of therapeutic options available, malignant melanoma remains a highly fatal disease, especially in its metastatic forms. The oncogenic role of protein tyrosine phosphatases (PTPs) is becoming increasingly clear, paving the way for novel antitumor treatments based on their inhibition. In this review, we present the oncogenic PTPs contributing to melanoma progression and we provide, where available, a description of new inhibitory strategies designed against these enzymes and possibly useful in melanoma treatment. Considering the relevance of the immune infiltrate in supporting melanoma progression, we also focus on the role of PTPs in modulating immune cell activity, identifying interesting therapeutic options that may support the currently applied immunomodulating approaches.
  • 1.2K
  • 13 Oct 2020
Topic Review
Fibroblast Subsets in Colorectal cancer
CAFs are defined as fibroblasts surrounding malignant tumor cells and are the most abundant cell type in the tumor microenvironment of colorectal cancer (CRC). CAFs consist of various functionally heterogeneous subsets which can promote or restrain cancer progression. Although most previous research has focused on the biology of epithelial cells, accumulating evidence shows that certain CAF subsets can also importantly contribute to tumor initiation and progression, thereby possibly providing avenues for improvement of clinical care for CRC patients. However, attention needs to be paid to comprehensive characterization and reporting of the subsets being investigated in CAF studies to enable more precise identification and targeting of “unfavorable” CAFs in advanced CRC.
  • 1.2K
  • 28 Jan 2021
Topic Review
Mast Cell Activation
Mast cell activation (MCA) may occur in different physiologic and pathologic conditions. Clinical symptoms resulting from MCA can be observed not only in the setting of allergic diseases, but even in the context of MC neoplasms. If MCA symptoms are severe and recurrent, the possibility of mast cell activation syndrome (MCAS) should be considered.
  • 1.2K
  • 12 Oct 2021
Topic Review
Poly ADP Ribose Polymerase Inhibitors
Poly ADP ribose polymerases (PARPs) are a family of enzymes that catalyse the transfer of ADP-ribose to target proteins, functioning in fundamental cellular processes including transcription, chromatin remodelling and DNA repair. PARP inhibitors (PARPis) including olaparib, niraparib and rucaparib are approved for the clinical management of women with ovarian cancer.
  • 1.2K
  • 12 Oct 2022
Topic Review
Impacts of COVID-19
SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its emergence. The COVID-19 pandemic has become widespread and known as a pathology of the respiratory system, affecting the ciliary epithelium at an early stage. In severe cases, COVID-19 can lead to development of lung disease: acute respiratory distress syndrome (ARDS). A variety of extrapulmonary symptoms may also occur, including acute renal failure (AKI); acute heart failure; coagulopathy; thromboembolic complications, including stroke and pulmonary embolism; and circulatory shock. The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus remains a global public health concern due to the systemic nature of the infection and its long-term consequences, many of which remain to be elucidated. SARS-CoV-2 targets endothelial cells and blood vessels, altering the tissue microenvironment, its secretion, immune-cell subpopulations, the extracellular matrix, and the molecular composition and mechanical properties.
  • 1.2K
  • 05 Jun 2023
Topic Review
Physiopathology of Mantle Cell Lymphoma
Mantle cell lymphoma (MCL) is a rare but aggressive B-cell hemopathy characterized by the translocation t(11;14)(q13;q32) that leads to the overexpression of the cell cycle regulatory protein cyclin D1. This translocation is the initial event of the lymphomagenesis, but tumor cells can acquire additional alterations allowing the progression of the disease with a more aggressive phenotype and a tight dependency on microenvironment signaling. To date, the chemotherapeutic-based standard care is largely inefficient and despite the recent advent of different targeted therapies including proteasome inhibitors, immunomodulatory drugs, tyrosine kinase inhibitors, relapses are frequent and are generally related to a dismal prognosis. As a result, MCL remains an incurable disease.
  • 1.2K
  • 18 Sep 2020
Topic Review
C-Src and EGFR Inhibition
The proto-oncogene c-Src is a non-receptor tyrosine kinase playing a key role in many cellular pathways, including cell survival, migration and proliferation. c-Src de-regulation has been observed in several cancer types, making it an appealing target for drug discovery efforts. Recent evidence emphasizes its crucial role not only in promoting oncogenic traits, but also in the acquisition and maintenance of cancer resistance to various chemotherapeutic or molecular target drugs. c-Src modulates epidermal growth factor receptor (EGFR) activation and amplifies its downstream oncogenic signals.
  • 1.2K
  • 27 Sep 2020
Topic Review
Nanoparticles-Based Targeted Drug Delivery
Several organic and inorganic nanoplatforms that have been designed exploiting the distinctive features of the tumor microenvironment and tumor cells offer favorable physicochemical properties and pharmacokinetic profiles of a parent drug, with delivery of higher amounts of the drug to the pathological site and its controlled release, thereby improving the balance between its efficacy and toxicity. Advances to this front have included the design and construction of targeted nanoparticles by conjugating homing devices like peptide, ligand, and Fab on the surface of nanomaterials to navigate nanoparticle drug complexes towards the target tumor cell with minimal destruction of healthy cells. Furthermore, actively targeting nanoparticles can facilitate the delivery and cellular uptake of nanoparticle-loaded drug constructs via binding with specific receptors expressed aberrantly on the surface of a tumor cell. Herein, we present an overview of the principle of targeted delivery approaches, exploiting drug-nanoparticle conjugates with multiple targeting moieties to target specific receptors of breast cancer cells and highlighting therapeutic evaluation in preclinical studies. We conclude that an understanding of the translational gap and challenges would show the possible future directions to foster the development of novel targeted nanotherapeutics. 
  • 1.2K
  • 11 Mar 2021
Topic Review
Multimeric PET Radioligands
Multimeric PET radioligands consist of identical binding motifs (pharmacophores) connected to a single backbone (linker) attached to a group, which can be labeled with a positron-emitting radionuclide suitable for PET molecular imaging (radiolabeled domain). 
  • 1.2K
  • 25 May 2021
Topic Review
Cytoskeleton Reorganization in EndMT
EndMT-derived cells, known as the myofibroblasts or cancer-associated fibroblasts (CAFs), are characterized by the loss of cell–cell junctions, loss of endothelial markers, and gain in mesenchymal ones.
  • 1.2K
  • 16 Nov 2021
Topic Review
Techniques for DNA Methylation Testing in Glioblastomas
Epigenetic changes in DNA methylation contribute to the development of many diseases, including cancer. In glioblastoma multiforme, the most prevalent primary brain cancer and an incurable tumor with a median survival time of 15 months, a single epigenetic modification, the methylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene, is a valid biomarker for predicting response to therapy with alkylating agents and also, independently, prognosis. The progress from single gene to whole-genome analysis of DNA methylation has allowed a better subclassification of glioblastomas.
  • 1.2K
  • 15 Jul 2022
Topic Review
Tenascin-C-Targeted Drug Delivery
Tenascin-C (TNC) is an extracellular matrix glycoprotein that participates in cell adhesion, growth, migration, and differentiation. TNC is expressed at a low level in healthy adult tissues, yet it is upregulated substantially and specifically in response to tissue injury.
  • 1.2K
  • 11 Dec 2020
Topic Review
Synergistically Anti-Multiple: Flavonoid, Non-Flavonoid Polyphenols, and Bortezomib
Multiple myeloma (MM) is a clonal plasma cell tumor originating from a post-mitotic lymphoid B-cell lineage. When two or more medications are combined to improve their therapeutic effects, this is referred to as drug synergism. For various diseases, including MM, appropriate drug combinations can reduce drug resistance or maximize efficacy. Bortezomib (BTZ), as a clinically used protease inhibitor, is a cornerstone of Velcade, Revlimid, and Dexamethasone (VRD).  Flavonoids and non-flavonoid polyphenols are potential supportive therapies to address some of the challenges faced in BTZ treatment. 
  • 1.2K
  • 22 Nov 2022
Topic Review
Grade 3 Neuroendocrine Tumors
Neuroendocrine neoplasms (NEN) are most often located in the lung and in the digestive tract. They are defined by the expression of specific biomarkers, such as synaptophysin and chromogranin A (CGA), which can be absent in high-grade NEN. Grade 3 Neuroendocrine Tumors are a subgroup of NEN presenting with well-differentiated morphology and high proliferation rate (Ki-67>20%).
  • 1.2K
  • 30 Jun 2021
Topic Review
Precision Anti-Cancer Medicines by Oligonucleotide in Clinical Reasearch
Oligonucleotide therapeutics enable a direct targeting of the gene by acting at the level of the RNA or at the level of the DNA, based on the Watson-Crick complementary rule of binding.
  • 1.2K
  • 29 Jul 2022
Topic Review
Antibody-Based Immunotherapy for Metastatic Melanoma
Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells.
  • 1.2K
  • 26 Oct 2020
Topic Review
Immune Microenvironment of Malignant Gliomas
Single-cell technologies allow precise identification of tumor composition at the single-cell level, providing high-resolution insights into the intratumoral heterogeneity and transcriptional activity of cells in the tumor microenvironment (TME) that previous approaches failed to capture. Malignant gliomas, the most common primary brain tumors in adults, are genetically heterogeneous and their TME consists of various stromal and immune cells playing an important role in tumor progression and responses to therapies. Previous gene expression or immunocytochemical studies of immune cells infiltrating TME of malignant gliomas failed to dissect their functional phenotypes. Single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) are powerful techniques allowing quantification of whole transcriptomes or >30 protein targets in individual cells. Both methods provide unprecedented resolution of TME. 
  • 1.2K
  • 17 Sep 2021
Topic Review
Revisiting Hepatic Artery Infusion Chemotherapy
Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results.
  • 1.2K
  • 29 Mar 2022
Topic Review
NRF2 Pathway
The NRF2 pathway represents one of the most intriguing pathways that promotes chemo- and radioresistance of neoplastic cells. Increasing findings suggest that the NRF2 signaling can be modulated by multiple epigenetic factors such as noncoding RNAs, which influence a large number of oncogenic mechanisms, both at transcriptional and at post-transcriptional levels. As a consequence, the identification and characterization of specific noncoding RNAs as biomarkers related to oxidative stress may help to clarify the relationship between them and NRF2 signaling in the tumor context, in terms of positive and negative modulation, also referring to their intersection with other NRF2 crosstalking pathways.
  • 1.2K
  • 18 Dec 2020
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