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Topic Review
Brain Barriers
Barriers between the brain and systemic circulation are dynamic and highly specialized to strictly regulate the access of a wide variety of molecules to the brain. These barriers allow for the delivery of nutrients and other molecules necessary for neuronal functioning, but often limit the permeation of xenobiotics, including drugs. In brain tumors, these barrier functions may be disrupted or altered. However, this disruption is often heterogeneous and not reliable to guaranteee the delivery of efficacious concentrations of antineoplastic agents to brain tumors.
  • 1.4K
  • 11 Jan 2021
Topic Review
Extracellular Matrix in Breast Cancer
The role of extracellular matrix in breast cancer progression has recently been realized. Here, the effect of various ECM properties including fiber structure, stiffness and biochemical composition are reviewed, with a special emphasis on the extracellular vesicles. 
  • 1.4K
  • 16 Oct 2020
Topic Review
DNA Damage/Repair Management in Cancers
DNA damage is well recognized as a critical factor in cancer development and progression. DNA lesions create an abnormal nucleotide or nucleotide fragment, causing a break in one or both chains of the DNA strand. When DNA damage occurs, the possibility of generated mutations increases. Genomic instability is one of the most important factors that lead to cancer development. DNA repair pathways perform the essential role of correcting the DNA lesions that occur from DNA damaging agents or carcinogens, thus maintaining genomic stability. Inefficient DNA repair is a critical driving force behind cancer establishment, progression and evolution. A thorough understanding of DNA repair mechanisms in cancer will allow for better therapeutic intervention.
  • 1.3K
  • 27 Oct 2020
Topic Review
FGFRs in Brain Tumors
Despite pharmacological treatments and surgical practice options, the mortality rate of astrocytomas and glioblastomas remains high, thus representing a medical emergency for which it is necessary to find new therapeutic strategies. Fibroblast growth factors (FGFs) act through their associated receptors (FGFRs), a family of tyrosine kinase receptors consisting of four members (FGFR1–4), regulators of tissue development and repair. In particular, FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, thus their gene alteration is certainly related to the development of the most common diseases, including cancer. FGFRs are subjected to multiple somatic aberrations such as chromosomal amplification of FGFR1; mutations and multiple dysregulations of FGFR2; and mutations, translocations, and significant amplifications of FGFR3 and FGFR4 that correlate to oncogenesis process. Therefore, the in-depth study of these receptor systems could help to understand the etiology of both astrocytoma and glioblastoma so as to achieve notable advances in more effective target therapies. Furthermore, the discovery of FGFR inhibitors revealed how these biological compounds improve the neoplastic condition by demonstrating efficacy and safety.
  • 1.3K
  • 29 Dec 2020
Topic Review
Approach to CALR-Positive Myeloproliferative Neoplasms
CALR mutations are a revolutionary discovery and represent an important hallmark of myeloproliferative neoplasms (MPN), especially essential thrombocythemia and primary myelofibrosis. To date, several CALR mutations were identified, with only frameshift mutations linked to the diseased phenotype. It is of diagnostic and prognostic importance to properly define the type of CALR mutation and subclassify it according to its structural similarities to the classical mutations, a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2 mutation), using a statistical approximation algorithm (AGADIR). Today, the knowledge on the pathogenesis of CALR-positive MPN is expanding and several cellular mechanisms have been recognized that finally cause a clonal hematopoietic expansion.
  • 1.3K
  • 06 May 2021
Topic Review
Nanomedicine in NSCLC
The hard diagnosis and treatment of NSCLC, together with its late diagnosis and lack of therapies during the early stages of the disease,  so far explain its high mortality rate. The reformulation of conventional therapies as nanomedicines, has led to a new generation of treatments for NSCLC. However, the deepening of the relationship between the tumor and the patient's immune system encompasses the most promising strategies today. From immune checkpoint inhibitors, identified in 2018, to the development of vaccines based on genetic material, immunotherapies represent the best of options. The use of nanometric vehicles for the release of genetic material, protein or drug allows reducing doses and increasing efficiency. These, together with delivery systems based on nanomedicines, promise to increase the specificity and efficacy of treatments, reducing the extremely harmful side effects of conventional therapies. Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related mortality. The heterogeneous nature of this disease hinders its diagnosis and treatment, requiring continuous advances in research aiming to understand its intricate nature. Consequently, the retrospective analysis of conventional therapies has allowed the introduction of novel tools provided by nanotechnology, leading to considerable improvements in clinical outcomes. Furthermore, the development of novel immunotherapies based on the recently understood interaction of the immune system with the tumor highlights the real possibility of definitively treating NSCLC from its early stages. Novel engineering approaches in nanomedicine will enable to overcome the intrinsic limits of conventional and emerging therapies regarding off-site cytotoxicity, specificity, resistance mechanisms, and administration issues. The convergence point of these therapies with nanotechnology lays the foundation for achieving currently unmet needs.
  • 1.3K
  • 17 Sep 2020
Topic Review
Prostate Cancer
Metastasis of prostate cancer often results in death of the patient. A cluster of fatty acid-binding protein (FABP) genes involved in transportation, accumulation and utilization of fatty acids are co-amplified and preferentially expressed in metastatic prostate cancer compared to localized disease. These genes, namely FABP12, FABP4, FABP9, FABP8 and FABP5, individually and collectively, promote properties associated with prostate cancer metastasis. Levels of these FABP genes may serve as an indicator of prostate cancer aggressiveness, and that inhibiting the action of FABP genes may provide a new approach to prevent and/or treat metastatic prostate cancer. 
  • 1.3K
  • 31 Dec 2020
Topic Review
Cofilin and Actin Dynamics
Proteins of the actin depolymerizing factor (ADF)/cofilin family are ubiquitous among eukaryotes and are essential regulators of actin dynamics and function. Mammalian neurons express cofilin-1 as the major isoform, but ADF and cofilin-2 are also expressed. All isoforms bind preferentially and cooperatively along ADP-subunits in F-actin, affecting the filament helical rotation, and when either alone or when enhanced by other proteins, promotes filament severing and subunit turnover.
  • 1.3K
  • 25 Oct 2021
Topic Review
Celiac Disease
Celiac disease (CD) is a chronic enteropathy that develops in genetically susceptible individuals after the ingestion of gluten. There has been a substantial increase in CD prevalence in the last 50 years, and it is now estimated that this disease affects approximately 1% of the population in the Western world. In the large majority of cases, CD is a benign disease, characterized by the complete resolution of symptoms and a normal life expectancy after the onset of a gluten-free diet (GFD). However, failure to adhere to a strict GFD bears the risk of adverse events and increases mortality. A considerable number of studies have considered the possible association between CD and neoplasms. In particular, an increased risk of malignancies, such as cancers of the gastrointestinal tract and intestinal lymphomas, has been reported. In this review, we summarize and discuss the current evidence on the possible association between CD and cancer.
  • 1.3K
  • 27 Oct 2020
Topic Review
Fc-Engineered Antibodies
Monoclonal antibody (mAb) therapy has rapidly changed the field of cancer therapy. In 1997, the CD20-targeting mAb rituximab was the first mAb to be approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer. Within two decades, dozens of mAbs entered the clinic for treatment of several hematological cancers and solid tumors, and numerous more are under clinical investigation. The success of mAbs as cancer therapeutics lies in their ability to induce various cytotoxic machineries against specific targets. These cytotoxic machineries include antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), which are all mediated via the fragment crystallizable (Fc) domain of mAbs. In this review article we will outline the novel approaches of engineering these Fc domains of mAbs to enhance their Fc-effector function and thereby their anti-tumor potency, with specific focus to summarize their (pre-) clinical status for the treatment of B-cell malignancies, including chronic lymphocytic leukemia (CLL), B-cell Non-Hodgkin lymphoma (B-NHL), and multiple myeloma (MM).
  • 1.3K
  • 01 Dec 2020
Topic Review
Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. The complex mechanism underlying the development and progression of PDAC includes interactions between genomic, epigenomic, and signaling pathway alterations. PDAC remains a devastating disease, despite extensive research efforts focused on the discovery of early diagnostic biomarkers and efficient therapeutic approaches, showing a high resistance to treatment that significantly contributes to poor survival. The success of epi-drugs in hematological malignancies and the robust body of evidence supporting the hypothesis about their ability to synergize with other anti-cancer drugs, sensitizing resistant tumor cells in preclinical models, have encouraged the search for these agents suitable for the future clinical management of PDAC.
  • 1.3K
  • 27 Oct 2020
Topic Review
Sacituzumab Govitecan in Breast Cancer
Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment.
  • 1.3K
  • 07 Dec 2021
Topic Review
Angiogenesis
Angiogenesis is an active process, regulating new vessel growth, and is crucial for the survival and growth of tumours next to other complex factors in the tumour microenvironment. We present possible molecular imaging approaches for tumour vascularisation and vitality, focusing on radiopharmaceuticals (tracers). Molecular imaging in general has become an integrated part of cancer therapy, by bringing relevant insights on tumour angiogenic status.
  • 1.3K
  • 16 Jun 2021
Topic Review
Cutaneous Melanoma
Cutaneous Melanoma (CM), arising from pigment-producing melanocytes in the skin, is an aggressive cancer with high metastatic potential. While cutaneous melanoma represents only a fraction of all skin cancers (<5%), it accounts for most skin-cancer-related deaths worldwide. Immune checkpoint inhibition has been the first therapeutic approach to significantly benefit patient survival after treatment. Nevertheless, the immunosuppressive tumor microenvironment and the intrinsic and acquired treatment resistance of melanoma remain crucial challenges. Combining local and systemic treatment offers the potential to augment therapeutic response and overcome resistance, although, complex drug combinations can harbor an increased risk of immune-related adverse events.
  • 1.3K
  • 22 Sep 2021
Topic Review
Glioblastoma
Glioblastoma (GBM) is the most popular primary central nervous system cancer and has an extremely expansive course. Aggressive tumor growth correlates with short median overall survival (OS) oscillating between 14 and 17 months. The survival rate of patients in a three-year follow up oscillates around 10%. The interaction of the proteins programmed death-1 (PD-1) and programmed cell death ligand (PD-L1) creates an immunoregulatory axis promoting invasion of glioblastoma multiforme cells in the brain tissue. The PD-1 pathway maintains immunological homeostasis and protects against autoimmunity. PD-L1 expression on glioblastoma surface promotes PD-1 receptor activation in microglia, resulting in the negative regulation of T cell responses. Glioblastoma multiforme cells induce PD-L1 secretion by activation of various receptors such as toll like receptor (TLR), epidermal growth factor receptor (EGFR), interferon alpha receptor (IFNAR), interferon-gamma receptor (IFNGR). Binding of the PD-1 ligand to the PD-1 receptor activates the protein tyrosine phosphatase SHP-2, which dephosphorylates Zap 70, and this inhibits T cell proliferation and downregulates lymphocyte cytotoxic activity. Relevant studies demonstrated that the expression of PD-L1 in glioma correlates with WHO grading and could be considered as a tumor biomarker. Studies in preclinical GBM mouse models confirmed the safety and efficiency of monoclonal antibodies targeting the PD-1/PD-L1 axis. Satisfactory results such as significant regression of tumor mass and longer animal survival time were observed. Monoclonal antibodies inhibiting PD-1 and PD-L1 are being tested in clinical trials concerning patients with recurrent glioblastoma multiforme.
  • 1.3K
  • 21 Apr 2021
Topic Review
BCL-2 Proteins in Pathogenesis
The ability to inhibit mitochondrial apoptosis is a hallmark of B-cell non-Hodgkin lymphomas (B-NHL). Activation of mitochondrial apoptosis is tightly controlled by members of B-cell leukemia/lymphoma-2 (BCL-2) family proteins via protein-protein interactions. Altering the balance between anti-apoptotic and pro-apoptotic BCL-2 proteins leads to apoptosis evasion and extended survival of malignant cells. The pro-survival BCL-2 proteins: B-cell leukemia/lymphoma-2 (BCL-2/BCL2), myeloid cell leukemia-1 (MCL-1/MCL1) and B-cell lymphoma-extra large (BCL-XL/BCL2L1) are frequently (over)expressed in B-NHL, which plays a crucial role in lymphoma pathogenesis, disease progression, and drug resistance. 
  • 1.3K
  • 23 Jun 2021
Topic Review
Lipid Metabolism and Melanoma Progression
Melanoma is a devastating skin cancer characterized by an impressive metabolic plasticity. Melanoma cells are able to adapt to the tumor microenvironment by using a variety of fuels that contribute to tumor growth and progression. In this review, the authors summarize the contribution of the lipid metabolic network in melanoma plasticity and aggressiveness, with a particular attention to specific lipid classes such as glycerophospholipids, sphingolipids, sterols and eicosanoids. They also highlight the role of adipose tissue in tumor progression as well as the potential antitumor role of drugs targeting critical steps of lipid metabolic pathways in the context of melanoma.
  • 1.3K
  • 13 Nov 2020
Topic Review
CXCL13 in Cancer and Other Diseases
C-X-C chemokine ligand 13 (CXCL13) and its receptor, CXCR5, make crucial contributions to this process by triggering intracellular signaling cascades in malignant cells and modulating the sophisticated TME in an autocrine or paracrine fashion. The CXCL13/CXCR5 axis has a dominant role in B cell recruitment and tertiary lymphoid structure formation, which activate immune responses against some tumors. In most cancer types, the CXCL13/CXCR5 axis mediates pro-neoplastic immune reactions by recruiting suppressive immune cells into tumor tissues. Tobacco smoke and haze (smohaze) and the carcinogen benzo(a)pyrene induce the secretion of CXCL13 by lung epithelial cells, which contributes to environmental lung carcinogenesis. 
  • 1.3K
  • 09 Dec 2021
Topic Review
Various Uses of Lycopene
Lycopene is a carotenoid abundantly found in red vegetables. This natural pigment displays an important role in human biological systems due to its excellent antioxidant and health-supporting functions, which show a protective effect against cardiovascular diseases, hypertension, cancers, and diabetes.
  • 1.3K
  • 28 Feb 2022
Topic Review
Drug Delivery Systems Polymeric Nanocarriers in Cancer Therapy
Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules that interact with DNA and cause cell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, and they can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specifically target cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs).
  • 1.3K
  • 25 Mar 2022
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