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Topic Review
Targeting Tryptophan Metabolism to Treat Cancers
Major hallmarks of cancers are connected to dysfunctions in many metabolic pathways aiming at providing the energetic needs and the raw material for cellular growth and the signaling molecules needed for oncogenesis. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions across many types of cancer. However, results from clinical trials assessing the benefit of inhibiting key limiting enzymes of this pathway such as indoleamine 2,3-dioxygenase (IDO1) or tryptophan 2,3-dioxygenase (TDO2) failed to meet the expectations. Bearing in mind the complexity of the tumoral terrain and the existence of different cancers with IDO1/TDO2 expressing and non-expressing tumoral cells, here we present a comprehensive analysis of the TRP global metabolic hub and the approach of inhibiting these pathways as a potential therapeutic option to treat cancers such as liver cancers. 
  • 511
  • 29 Mar 2022
Topic Review
Targeting Tie2 in the Tumor Microenvironment
The dissemination of cancer cells from their original location to distant organs where they grow, a process called metastasis, causes more than 90% of cancer deaths. The identification of the molecular mechanisms of metastasis and the development of anti-metastatic therapies are essential to increase patient survival. In recent years, targeting the tumor microenvironment has become a promising avenue to prevent both tumor growth and metastasis. As the tumor microenvironment contains not only cancer cells but also blood vessels, immune cells, and other non-cancerous cells, it is naïve to think that therapy only affects a single cell type in this complex environment. Here to stress the importance, and ways to inhibit the function, of one therapeutic target: the receptor Tie2. Tie2 is a receptor present on the cell surface of several cell types within the tumor microenvironment and regulates tumor angiogenesis, growth, and metastasis to distant organs.
  • 562
  • 06 Dec 2021
Topic Review
Targeting Strategies against Radioresistant Tumors
A radiosensitizer is a drug that makes cancer cells more sensitive to radiation therapy. These compounds apparently promote the scavenging of free radicals produced by radiation damage on the molecular level. Radiation therapy generally affects DNA; mainly, it leads to DNA DSBs. Therefore, many radiosensitizing agents have been formulated to target the clinically developed DNA DSB repair pathways. Other agents instead target different pathways, e.g., DNA-PKcs, ATM, and ATR signaling cascades. More than seven PARP inhibitors, for example, are currently being developed considering their role in DNA repair, especially for tumors with DNA repair defects, such as BRCA mutation, because of their synthetic lethality.
  • 406
  • 16 Sep 2022
Topic Review
Targeting Signalling Pathways in Chronic Wound Healing
Chronic wounds fail to achieve complete closure and are an economic burden to healthcare systems due to the limited treatment options and constant medical attention. Chronic wounds are characterised by dysregulated signalling pathways.
  • 151
  • 04 Jan 2024
Topic Review
Targeting Protein Aggregates with Natural Products
Protein aggregation is one of the hallmarks of aging and aging-related diseases, especially for the neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and others.
  • 256
  • 21 Jul 2023
Topic Review
Targeting Potential in Gliomas
Gliomas portray a large and heterogeneous group of CNS tumors, encompassing a wide range of low- to high-grade tumors, as defined by histological and molecular characteristics. The identification of signature mutations and other molecular abnormalities has largely impacted tumor classification, diagnosis, and therapy. Transcription factors (TFs) are master regulators of gene expression programs, which ultimately shape cell fate and homeostasis. A variety of TFs have been detected to be aberrantly expressed in brain tumors, being highly implicated in critical pathological aspects and progression of gliomas.
  • 345
  • 18 Apr 2022
Topic Review
Targeting Post-Translational Modifications in Lung Cancer
Lung cancer is one of the most common cancers worldwide. It consists of two different subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Despite novel therapeutic options such as immunotherapy, only 20% of lung cancer patients survive the disease after five years. This low survival rate is due to acquired drug resistance and severe off-target effects caused by currently used therapies. Identification and development of novel and targeted therapeutic approaches are urgently required to improve the standard of care for lung cancer patients.
  • 751
  • 09 Jan 2023
Topic Review
Targeting Platelet Activation in Abdominal Aortic Aneurysm
Abdominal aortic aneurysm (AAA) is defined as permanent dilatation of the abdominal aorta, which most commonly occurs in the infrarenal region in humans. Abdominal aortic aneurysm is a potentially fatal vascular disease that involves complex multifactorial hemodynamic, thrombotic, inflammatory, and aortic wall remodeling processes. However, its mechanisms are incompletely understood. It has become increasingly clear that platelets are involved in pathological processes of vascular diseases beyond their role in hemostasis and thrombosis. Platelet activation with membrane receptors and secreted mediators promotes thrombus formation and the accumulation of inflammatory cells, which may play an important role in the development of AAA by destroying the structural integrity and stability of the vessel wall. Turbulent blood flow in aortic aneurysms promotes platelet activation and aggregation. Platelet count and heterogeneity are important predictive, diagnostic, and prognostic indicators of AAA.
  • 439
  • 21 Feb 2022
Topic Review
Targeting PAI-1 for Potential Therapies
Hypofibrinolysis is a key abnormality in diabetes and contributes to the adverse vascular outcome in this population. Plasminogen activator inhibitor (PAI)-1 is an important regulator of the fibrinolytic process and levels of this antifibrinolytic protein are elevated in diabetes and insulin resistant states. This review describes both the physiological and pathological role of PAI-1 in health and disease, focusing on the mechanism of action as well as protein abnormalities in vascular disease with special focus on diabetes. Attempts at inhibiting protein function, using different techniques, are also discussed including direct and indirect interference with production as well as inhibition of protein function. Developing PAI-1 inhibitors represents an alternative approach to managing hypofibrinolysis by targeting the pathological abnormality rather than current practice that relies on profound inhibition of the cellular and/or acellular arms of coagulation, and which can be associated with increased bleeding events. The review offers up-to-date knowledge on the mechanisms of action of PAI-1 together with the role of altering protein function to improve hypofirbinolysis. Developing PAI-1 inhibitors may form for the basis of future new class of antithrombotic agents that reduce vascular complications in diabetes.
  • 819
  • 31 May 2021
Topic Review
Targeting p53 in Colorectal Cancer
p53, a critical tumor suppressor, is commonly mutated in neoplasia, including colorectal cancer. To devise anti-cancer strategies targeting p53, it is crucial to understand the myriad cell-specific regulatory mechanisms in the p53 signaling pathway, and how these same regulatory mechanisms may be evaded by p53 mutants.
  • 474
  • 18 Jan 2022
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