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Topic Review
Immunotherapy for Cutaneous Malignant Melanoma
Malignant melanoma (mM) is the leading cause of death among cutaneous malignancies. While its incidence is increasing, the most recent cancer statistics show a small but clear decrease in mortality rate. This trend reflects the introduction of novel and more effective therapeutic regimens, including the two cornerstones of melanoma therapy: immunotherapies and targeted therapies. Unlike chemotherapies or radiation, in which the therapy directly induces cancer cell death, immunotherapies stimulate the patient’s immune system to control and eliminate the tumor. Advantages of immunotherapies over traditional cancer treatments include increased durability for long-term control or even cure and more precisely targeted anti-tumor activity that spares healthy tissues, many times with comparable or even reduced overall toxicity. The high immunogenicity and somatic mutation burden of melanoma likely contribute to the success of immunotherapy. Treatments combining immunotherapies with targeted therapies, which disable the carcinogenic products of mutated cancer cells, have further increased treatment efficacy and durability. Toxicity and resistance, however, remain critical challenges to the field. There are three types of immunotherapies currently approved by the US Food and Drug Administration (FDA) for the treatment of advanced melanoma: (1) T-cell stimulating cytokines (i.e. interferon (IFN)-α2b and interleukin-2 (IL-2)); (2) T-cell exhaustion-mitigating immune checkpoint inhibitors (ICI); and (3) a dendritic cell (DC)-activating oncolytic virus (T-VEC). Still others, such as adoptive cell transfer (ACT), hold strong promise for the future.
  • 497
  • 20 Apr 2022
Topic Review
Heterogeneity Sources in Metabolic Dysfunction-Associated Fatty Liver Disease
Non-alcoholic fatty liver disease (NAFLD) is a slowly progressing disease, beginning with isolated liver steatosis that evolves in a subset of patients to non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. 
  • 496
  • 24 Jan 2022
Topic Review
Ruthenium Complexes
Ruthenium(Ru)-complexes go beyond the limitations of Platinum(Pt)-based drugs, notably oxaliplatin, and exhibit higher potency while offering less toxicity in colorectal cancer (CRC) treatment. Therefore, Ru-complexes can be a promising alternative to oxaliplatin in CRC treatment. 
  • 495
  • 08 Sep 2021
Topic Review
MRNA Therapies
Currently, mRNA appears as a very promising and innovative therapeutic approach for diseases associated with functional loss of proteins, through the administration of a synthetic mRNA, which promotes the reestablishment of protein levels and restores its function. Moreover, mRNA can create new cellular functions, for example for passive immunization, allowing to stimulate the immune system, through the translation of antigenic mRNA for specific cell recognition (e.g., cancer cells) or antibody production. The fact that a relatively small amount of encoded antigen, from a synthetic mRNA, can be sufficient to obtain robust signs of efficacy, is one of the main advantages of using this biomolecule in immunotherapy. However, the global success of such mRNA-based treatments depends on a high number of these biomolecules and an effective in vivo delivery to target cells involved in a given disease. After proving that in vivo mRNA administration is possible and viable, the concept of using mRNA as a therapeutic basis was readily accepted and used in a variety of diseases, including diabetes, HIV infection, anemia, hemophilia, myocardial infarction, cancer, asthma, metabolic disorders, fibrosis, skeletal degeneration and neurological disorders, such as Friedreich’s ataxia and Alzheimer’s disease.
  • 495
  • 04 Jan 2022
Topic Review
Histone Deacetylases in Human Cancers
Histone modification is an essential mark in maintaining cellular memory and, therefore, loss of this mark can lead to tumor transformation. As these epigenetic changes are reversible, the use of molecules that can restore the functions of the enzymes responsible for the changes is therapeutically necessary. Natural molecules, mainly those isolated from medicinal plants, have demonstrated significant inhibitory properties against enzymes related to histone modifications, particularly histone deacetylases (HDACs). Flavonoids, terpenoids, phenolic acids, and alkaloids exert significant inhibitory effects against HDAC and exhibit promising epi-drug properties. This suggests that epi-drugs against HDAC could prevent and treat various human cancers. 
  • 495
  • 20 Apr 2022
Topic Review
Uses of Traditional Plants for Diabetes Nephropathy
Diabetic nephropathy (DN) is a serious kidney illness characterized by proteinuria, glomerular enlargement, reduced glomerular filtration, and renal fibrosis. DN is the most common cause of end-stage kidney disease, accounting for nearly one-third of all cases of diabetes worldwide.
  • 495
  • 08 Jul 2022
Topic Review
Drugs of the Kallikrein–Kinin System
The kallikrein–kinin system consists of the two kininogen substrates present in the blood plasma, and two serine proteases: the plasma and tissue kallikreins. The action of the latter on kininogens produces small peptides, the kinins, short-lived, but endowed by powerful pharmacologic actions on blood vessels and other tissues. Several classes of drugs alter kinin formation or action at their receptors for a therapeutic benefit.
  • 494
  • 17 Jul 2023
Topic Review Video
Exosomes as Nanosystems of Nucleic Acids and Drugs
Exosomes are defined as a type of extracellular vesicle released when multivesicular bodies of the endocytic pathway fuse with the plasma membrane. They are characterized by their role in extracellular communication, partly due to their composition, and present the ability to recognize and interact with cells from the immune system, enabling an immune response. Their targeting capability and nanosized dimensions make them great candidates for cancer therapy. As chemotherapy is associated with cytotoxicity and multiple drug resistance, the use of exosomes targeting capabilities, able to deliver anticancer drugs specifically to cancer cells, is a great approach to overcome these disadvantages. 
  • 493
  • 21 Nov 2022
Topic Review
Megalin
Megalin, a recently discovered endocytic receptor for prorenin and renin, not only contributes to renin/prorenin reabsorption in the proximal tubule of the kidney, but simultaneously plays a role in renal Ang II generation, although how exactly this occurs is still unknown . 
  • 492
  • 11 Nov 2021
Topic Review Video
Allosteric Antagonism of the Pregnane X Receptor
The pregnane X receptor (PXR, NR1I2) is a xenobiotic-activated transcription factor with high levels of expression in the liver. It not only plays a key role in drug metabolism and elimination, but also promotes tumor growth, drug resistance, and metabolic diseases. It has been proposed as a therapeutic target for type II diabetes, metabolic syndrome, and inflammatory bowel disease, and PXR antagonists have recently been considered as a therapy for colon cancer. The identified allosteric sites of the PXR provide new insights into the development of safe and efficient allosteric modulators of the PXR receptor. Researchers therefore propose that novel PXR allosteric sites might be promising targets for treating chronic metabolic diseases and some cancers. 
  • 492
  • 13 Oct 2022
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