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Topic Review
New Frontier of Targeted Immunotherapy in Multiple Myeloma
The approval of monoclonal antibody (MoAb) against CD38 (daratumumab) and SLAMF7 (elotuzumab) in relapsed and refractory MM (RRMM) represents an important milestone in the development of targeted immunotherapy in MM. These MoAb-based agents significantly induce cytotoxicity of MM cells via multiple effector-dependent mechanisms and can further induce immunomodulation to repair a dysfunctional tumor immune microenvironment. 
  • 604
  • 27 Dec 2021
Topic Review
Bispecific Antibodies for IFN-β Delivery to ErbB2+ Tumors
The main aim of this work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb.
  • 604
  • 29 Mar 2022
Topic Review
Metformin in Breast Cancer
Metformin is a widely prescribed oral antidiabetic medication. This biguanide is considered a first-line drug for the management of type 2 diabetes (T2D). Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among women worldwide. Type 2 diabetes–associated metabolic traits such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are well-known risk factors for breast cancer.
  • 604
  • 21 Mar 2022
Topic Review
Breast carcinoma eukaryotic initiation factors
Breast cancer is the most frequent neoplasm in females. It is a heterogenous entity, classified into intrinsic subtypes based on gene expression data and in corresponding clinical subtypes based on the determination of hormone receptor expression and proliferative activity estimated from ki67 by immunohistochemistry. As for other tumors, the metabolism of breast tumors depends on aerobic glycolysis ("Warburg-effect") and the capability for effective biosynthesis of proteins. Quantity and quality of protein biosynthesis is mainly controlled in the initiation phase of translation, which is characterized by a complex interaction of eucaryotic initiation factors with the mRNA and ribosomal proteins to form a translationally active ribosome. Thus the eIF subunit composition varies from cancer to cancer and is a key factor for determining the cancer cell´s proteome. eIFs can therefore become a suitable anti-cancer drug target. We here summarize the current knowledge on eIF expression and prognostic impact in breast cancer.
  • 603
  • 11 Aug 2020
Topic Review
UM-EVs involved in tumor progression
Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.
  • 603
  • 04 Apr 2021
Topic Review
Multidrug Resistance Mechanisms and Nano-Treatments
The cellular mechanisms of drug resistance prevent the correct efficacy of the therapies used in various types of cancer and nanotechnology has been postulated as a possible alternative to avoid them. This entry focuses on describing the different mechanisms of drug resistance and dis-covering which nanotechnology-based therapies have been used in recent years to evade them in colon (CRC) and pancreatic cancer (PAC). Here we summarize the use of different types of nanotechnology (mainly nanoparticles) that have shown efficacy in vitro and in vivo in preclinical phases, allowing future in-depth research in CRC and PAC and its translation to future clinical trials.
  • 603
  • 02 May 2021
Topic Review
D Adenovirus Oncolytic Viral Vectors
Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.
  • 603
  • 22 Sep 2021
Topic Review
Neuroendocrine Tumors
Neuroendocrine neoplasms (NENs) first described as “karzinoide” by Dr. Oberndorfer in 1907, comprise a family of heterogeneous tumors which can range from well differentiated neuroendocrine tumors (NETs) to poorly differentiated neuroendocrine carcinomas (NECs). NENs emerge from the diffuse endocrine systemand therefore can be found throughout the body, but they most commonly occur in the gastrointestinal tract with a peak incidence around the 5th and 6th decade of life. Based on the latest Survival Epidemiology and End Results data, incidence of NENs is on the rise with almost 7 cases per 100,000 persons in the United States. NENs can be alternatively classified as functional or non-functional based on the release of specific hormones by the tumor cells (e.g., serotonin, vasoactive intestinal peptide, insulin, gastrin, somatostatin, glucagon) and the subsequent development of various secretory syndromes.
  • 603
  • 16 Dec 2021
Topic Review
Cancer-Associated Fibroblasts in Cholangiocarcinoma
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis.
  • 603
  • 10 Nov 2022
Topic Review
ESR1 Mutations
The ESR1 gene located at 6q25.1–q25.2 encodes an ER and a ligand-activated transcription factor consisting of several domains involved in hormone binding.
  • 602
  • 18 Dec 2020
Topic Review
CAR T-Cells for CNS Lymphoma
Primary or secondary central nervous system (CNS) lymphoma is frequently associated with a poor prognosis. CAR T-cells are being established as a relevant treatment approach in hematological B-cell malignancies. Unfortunately, most clinical studies on chimeric antigen-receptor (CAR) T-cells have excluded patients with CNS involvement but several clinical trials on CAR T-cell therapy in CNS lymphoma patients are currently ongoing. Preclinical and preliminary clinical data suggest an overall acceptable safety profile and considerable anti-tumor effects might be extrapolated for CAR T-cell therapy in CNS lymphoma. 
  • 602
  • 01 Jun 2021
Topic Review
Designer T and NK Cells in Glioblastoma Immunotherapy
Glioblastoma (GBM) is the most prevalent, aggressive primary brain tumour with a dismal prognosis. Gene editing technologies are a game changer, enabling design of novel molecular-immunological treatments to be used in combination with chemoradiation, to achieve long lasting survival benefits for patients. Designer T and NK cells are a modality within immunotherapy that manipulates receptor-ligand interactions to enhance cells of the immune system to destroy cancer more effectively. Patient’s own immune cells are isolated, genetically modified to improve responses against cancer cells, expanded, and subsequently reintroduced into the individual.
  • 602
  • 29 Mar 2022
Topic Review
Metabolic Reprogramming in Thyroid Cancer
Reprogramming of metabolism is now recognized a hallmark of carcinogenesis as metabolic changes, such as those related to glucose, glutamine and lipids, are tightly related to the proliferation, invasion, migration, radiosensitivity, and chemosensitivity of several tumors, including thyroid cancer.
  • 602
  • 29 Mar 2022
Topic Review
DPP-IV Inhibition in Anticancer Treatment
Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nevertheless, the modulation of the bioavailability and function of other DPP-IV substrates, including chemokines, raises the possibility that the use of these orally administered drugs with favorable side-effect profiles might be extended beyond the treatment of hyperglycemia. 
  • 602
  • 05 May 2022
Topic Review
Role of Endoscopy in Upper Gastrointestinal Cancers
Upper gastrointestinal (GI) malignancy is a leading cause of cancer-related morbidity and mortality. Upper endoscopy has an established role in diagnosing and staging upper GI cancers, screening for pre-malignant lesions, and providing palliation in cases of advanced malignancy. New advances in endoscopic techniques and technology have improved diagnostic accuracy and increased the therapeutic potential of upper endoscopy.
  • 602
  • 16 Jan 2023
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. 
  • 601
  • 23 Jun 2021
Topic Review
Superparamagnetic Iron Oxide Nanoparticles in Cancer Therapy
Despite significant advances in cancer therapy, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able to handle the requirements of the clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have been at the forefront of nanotechnology development since the mid-1990s, thanks to their former role as contrast agents for magnetic resonance imaging. Though their use as MRI probes has been discontinued due to an unfavorable cost/benefit ratio, several innovative applications as therapeutic tools have prompted a renewal of interest. The unique characteristics of SPION, i.e., their magnetic properties enabling specific response when submitted to high frequency (magnetic hyperthermia) or low frequency (magneto-mechanical therapy) alternating magnetic field, and their ability to generate reactive oxygen species (either intrinsically or when activated using various stimuli), make them particularly adapted for cancer therapy.
  • 601
  • 29 Jan 2023
Topic Review
Therapy for Brain Metastases
This manuscript reviews the impact of tumor biology and molecular profiles on the management paradigm for BM patients and critically analyzes the current landscape of SRS, with a specific focus on integration with systemic therapy. We also discuss emerging treatment strategies combining SRS and ICIs, the impact of timing and the sequencing of these therapies around SRS, the effect of corticosteroids, and review post-treatment imaging findings, including pseudo-progression and radiation necrosis.
  • 600
  • 29 Mar 2022
Topic Review
A Disintegrin and Metalloproteinase (ADAM) Family
A disintegrin and metalloproteinase (ADAM) proteins are proteolytic enzymes that are responsible for destroying the extracellular matrix, but they also have adhesive properties. Recent investigations have demonstrated that the expression of several ADAMs is upregulated in gastrointestinal (GI) tumour cells and have linked the secretion of these proteins to pathogenesis of GI malignancies.
  • 600
  • 18 May 2022
Topic Review
Regulators of p53 Acetylation
The tumor suppressor p53 is a transcription factor that regulates the expression of dozens of target genes and diverse physiological processes. To precisely regulate the p53 network, p53 undergoes various post-translational modifications and alters the selectivity of target genes. Acetylation plays an essential role in cell fate determination through the activation of p53. p53 acts as a transcriptional factor that regulates more than 200 target genes and exerts a number of biological effects. Post-translational modifications play an essential role in the precise regulation of the selectivity of different target genes and subsequent physiological outcomes.
  • 600
  • 08 Dec 2022
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