Current Drug Targets - Volume 25, Issue 3, 2024

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and commonly occurs in the Caucasian population. The malignancy involves the uvea of the eye, which includes the iris, ciliary body, and choroid. The etiology of UM is still not well understood, but age is a risk factor. Symptoms include blurred vision, redness of the eye, floaters, dark spots, a change in the size of the pupil, and loss of vision. The location, shape, and size of the tumor are important for therapeutic purposes. Treating metastasis is always a challenge in UM cases. In cases of lung metastasis, the survival rate decreases. Treatment includes surgery, laser therapy, immunotherapy, hormone therapy, and chemotherapy. Recently, in 2022, the United States Food and Drug Administration (FDA) approved the drug tebentafusp. Tebentafusp was developed to target the most common HLA complex in humans. The present review discusses the indications for the use of a new drug tebentafusp, its mechanism of action, dose, pharmacokinetics, results of clinical trials conducted, and adverse effects like cytokine release syndrome. Hence, tebentafusp is the first T cell receptor (TCR) therapeutic drug that could be considered for the treatment of UM.

Bile acids play important roles in the human body, and changes in their pool can be used as markers for various liver pathologies. In addition to their functional effects in modulating inflammatory responses and cellular survivability, the unconjugated or conjugated, secondary, or primary nature of bile acids accounts for their various ligand effects. The common hydrophilic bile acids have been used successfully as local treatment to resolve drug-induced cell damage or to ameliorate hearing loss. From various literature references, bile acids show concentration and tissue-dependent effects. Some hydrophobic bile acids act as ligands modulating vitamin D receptors, muscarinic receptors, and calcium-activated potassium channels, important proteins in the inner ear system. Currently, there are limited resources investigating the therapeutic effects of bile acid on hearing loss and little to no information on detecting bile acids in the remote ear system, let alone baseline bile acid levels and their prevalence in healthy and disease conditions. This review presents both hydrophilic and hydrophobic human bile acids and their tissue-specific effects in modulating cellular integrity, thus considering the possible effects and extended therapeutic applicability of bile acids to the inner ear tissue.

There exists a huge number of patients suffering from chronic liver disease worldwide. As a disease with high incidence and mortality worldwide, strengthening the research on the pathogenesis of chronic liver disease and the development of novel drugs is an important issue related to the health of all human beings. Phosphorylation modification of proteins plays a crucial role in cellular signal transduction, and phosphatases are involved in the development of liver diseases. Therefore, this article summarized the important role of protein phosphatases in chronic liver disease with the aim of facilitating the development of drugs targeting protein phosphatases for the treatment of chronic liver disease.

Physiologically, cytokines play an extremely important role in maintaining cellular and subcellular homeostasis, as they interact almost with every cell in the organism. Therefore, cytokines play a significantly critical role in the field of pathogenic pharmacological therapy of different types of pathologies. Cytokine is a large family containing many subfamilies and can be evaluated into groups according to their action on epithelial cell proliferation; stimulatory include transforming growth factor-α (TGF-α), Interlukine-22 (IL-22), IL-13, IL-6, IL-1RA and IL-17 and inhibitory include IL-1α, interferon type I (IFN type I), and TGF-β. The balance between stimulatory and inhibitory cytokines is essential for maintaining normal epithelial cell turnover and tissue homeostasis. Dysregulation of cytokine production can contribute to various pathological conditions, including inflammatory disorders, tissue damage, and cancer. Several cytokines have shown the ability to affect programmed cell death (apoptosis) and the capability to suppress non-purpose cell proliferation. Clinically, understanding the role of cytokines' role in epithelial tissue is crucial for evaluating a novel therapeutic target that can be of use as a new tactic in the management of carcinomas and tissue healing capacity. The review provides a comprehensive and up-to-date synthesis of current knowledge regarding the multifaceted effects of cytokines on epithelial cell proliferation, with a particular emphasis on the intestinal epithelium. Also, the paper will highlight the diverse signaling pathways activated by cytokines and their downstream consequences on epithelial cell division. It will also explore the potential therapeutic implications of targeting cytokine- epithelial cell interactions in the context of various diseases.

Breast cancer is a widespread condition that kills more women from cancer-related causes than any other type of cancer globally. Women who have estrogen-dependent, initial metastatic breast cancer frequently receive treatment with surgery, radiation therapy, and chemotherapy. They may also get more specialized treatments like tamoxifen or aromatase inhibitors (anastrozole or letrozole). The World Health Organisation reported in 2012 that by 2030, breast cancer will be more common worldwide. There are several phytochemicals, such as isoflavones, coumestans, lignans, and prenylflavonoides. Isoflavones have been shown in studies to prevent the spread of breast cancer and to trigger apoptosis. Targeting BCs in metastatic breast cancer may be made possible by combining well-formulated phytochemicals in nanoparticles or other novel drug delivery agents with currently accepted endocrine and/or conventional chemotherapies. Cell signaling, regulation of cell cycles, oxidative stress action, and inflammation could be positively impacted by phytoconstituents. They have the ability to alter non-coding RNAs, to prevent the proliferation and regeneration of cancer cells. The availability of novel approaches helps in disease targeting, safety, effectiveness and efficacy. The current literature helps to know the available drugs i.e. phytoconstituents or novel drug delivery like nanoparticle, microsphere, micelles, liposomes and neosomes. The literature has been taken from PubMed, Google Scholar, SciFinder, or other internet sites.