Topic Review
Arginine Signaling and Cancer Metabolism
Arginine is an amino acid critically involved in multiple cellular processes including the syntheses of nitric oxide and polyamine, and is a direct activator of mTOR, a nutrient sensing kinase strongly implicated in carcinogenesis. In this review, we will discuss arginine as a signaling metabolite, arginine’s role in cancer metabolism, arginine as an epigenetic regulator, arginine as an immunomodulator, and arginine as a therapeutic target. The different cell killing mechanisms associated with various cancer types will also be described.
  • 26329
  • 29 Mar 2022
Topic Review
Monochromatic X-rays
Monochromatic X-ray has a single energy level in contrast to white X-rays used in conventional radiation therapy. Irradiation of high Z elements such as gadolinium, gold and silver with a monochromatic X-ray can result in photoelectric effects that includes the release of the Auger electrons that have strong cell killing effect. To apply this principle to cancer therapy, various nanoparticles loaded with high Z elements have been developed that enabled high Z elements to be delivered to tumor. The recent addition is gadolinium-loaded mesoporous silica nanoparticle (Gd-MSN). Tumor spheroids have been used as a convenient tumor model to demonstrate that monochromatic X-rays with energy level at or higher than the K-edge energy of gadolinium can destruct tumor mass that has Gd-MSN distributed throughout tumor spheroids.
  • 3094
  • 22 Jul 2020
Topic Review
Universal Model of Cancer Transformation and Development
As a phenomenon, cancer is a disease related to multicellular evolution, i.e., cancer in general is understood to be a failure of the multicellular systems and is considered a reversal to unicellularity. Cancer cells are like unicellular organisms that benefit from ancestral-like traits. As a disease, cancer can be interpreted as (a) a destruction of cooperative behaviors underlying multicellular evolution, (b) a disruption of molecular networks established during the emergence of multicellularity or (c) an atavistic state resulting from reactivation of primitive programs typical of the earliest unicellular species. From this point of view and in accordance with the layered model of evolution of cellular functionalities, cancer transformation can occur as a result of huge disturbances or the destruction of functionalities that are located in the multicellular layer.
  • 2027
  • 06 May 2022
Topic Review
Tumoroid
The term “tumoroid” means “tumor-like organoid”: tumoroids typically derive from primary tumors harvested from oncological patients and they can mimic human tumor microenvironment (TME); nowadays, they are considered a promising tool for cost-effective studies on novel anticancer drugs to be used in precision medicine in the field of oncology.
  • 1580
  • 01 Sep 2020
Topic Review
Antibody–Drug Conjugates
An armed antibody or antibody–drug conjugate (ADC) is a vectorized chemotherapy, which results from the grafting of a cytotoxic agent onto a monoclonal antibody via a judiciously constructed spacer arm. ADCs have made considerable progress in 10 years. While in 2009 only gemtuzumab ozogamicin (Mylotarg®) was used clinically, in 2020, 9 Food and Drug Administration (FDA)-approved ADCs are available, and more than 80 others are in active clinical studies. This review will focus on FDA-approved ADCs, their limitations including their toxicity and associated resistance mechanisms, as well as new emerging strategies to address these issues and attempt to widen their therapeutic window. Finally, we will discuss their combination with conventional chemotherapy or checkpoint inhibitors, to allow ADCs to get a little closer to the magic bullet imagined by Paul Ehrlich at the beginning of the 20th century.
  • 1512
  • 10 Apr 2021
Topic Review
Exploiting Proteotoxic Stress in Cancer
Cancer cells typically have elevated proteotoxic stress as a result of genomic instability. The disruption of protein homeostasis causes endoplasmic reticulum stress. If not promptly managed, it could lead to a global decline in cellular function and eventual cell death[1]. This summary of review explores different protein quality control pathways and the translation of drugs targeting proteotoxic stress in haematologic cancers (using multiple myeloma as an example) versus solid cancers (using Triple Negative Breast Cancer as an example).
  • 1202
  • 30 Oct 2020
Topic Review
Cancer-Associated Thrombosis Patients with Glioblastoma
Cancer is an independent risk factor for the development of venous thromboembolism (VTE). Glioblastomas are amongst cancer types with the most thrombogenic potential and patients are at a particularly high risk of VTE with an incidence up to 20–30% per year. Currently, major efforts are underway to gain novel insights into risk factors and pathomechanisms to provide a better understanding of development of VTE in patients with primary brain tumors. Treatment of VTE requires therapeutic anticoagulation, which accordingly to recently-published guidelines should be performed using low molecular weight heparin or, in case of low bleeding risk, using a direct oral anticoagulant. However, this can be very challenging due to an increased risk of intracranial hemorrhage in this patient group. Furthermore, limited data are available on the subgroup of patients with primary brain tumors.
  • 1025
  • 13 Oct 2020
Topic Review
Angiogenesis and de novo Arteriogenesis
Arteriogenesis supply oxygen and nutrients in tumor microenvironment (TME), which may play an important role in tumor growth and metastasis. Current anti-angiogenetic targeted treatments have not shown substantial clinical benefits and they are poorly tolerated, and even lead to more malignant relapse. The heterogeneity of tumor-associated endothelial cells (TAECs) and tumor vasculature may be important and should be appreciated in therapeutic targeting the TME. In this regard, the de novo arteriogenesis within the TME may be associated with tumor progression, stemness of cancer stem-like cells (CSCs) and therapeutic resistance and relapse. Targeting tumor arteriogenesis may thus be a potential novel therapeutic target. Specifically, targeting the FoxO1-CD36-Notch pathway could show the clinical potential by acting on arteriolar niche and CSCs at the same time in a variety of cancers including neuroendocrine cancers, breast cancers, lung cancers and malignant melanoma.
  • 904
  • 29 Oct 2020
Topic Review
Satellitosis in Neurological Disease
The secondary structures of Scherer commonly known as perineuronal and perivascular satellitosis have been identified as a histopathological hallmark of diffuse, invasive, high-grade gliomas. They are recognised as perineuronal satellitosis when clusters of neoplastic glial cells surround neurons cell bodies and perivascular satellitosis when such tumour cells surround blood vessels infiltrating Virchow–Robin spaces. 
  • 896
  • 27 Jan 2021
Topic Review
P53 Protein famliy
p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li–Fraumeni syndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 is degraded. Despite the ongoing efforts, the treatment of cancers remains challenging. Presently, the endeavors focus on reactivating p53 exclusively, neglecting the potential of the restoration of p73 protein for cancer eradication. Taken that several small molecules reactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53 proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 and describes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancer therapy.
  • 831
  • 21 Oct 2020
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