Targets, Volume 3, Issue 3 (September 2025) – 6 articles

Chordomas are primary tumors of the skull base and vertebral column typically derived from the notochord. Treatment options consist of surgical resection, radiotherapy, and chemotherapy. This study reviews clinical trials focused on radiotherapy techniques, such as photon therapy and carbon ion radiotherapy, as well as the concomitant use of radia-tion sensitizers. We completed a literature review on all published clinical trials on the usage of photon, proton, and carbon ion radiotherapy (CIRT) for chordoma in adults and all published literature on radiation sensitizers used for treatment in chordoma from 2000 to 2025. We reviewed all nine current clinical trials on radiotherapy for chordoma in adults. All clinical trials were able to achieve an overall survival rate above 50% at 3-year follow-up. Seven publications were found on the use of radiation sensitizers for chordomas, both in vitro and in vivo. The completed clinical trials evaluate the effectiveness of proton, photon, and CIRT for treatment of the skull base, spine, and sacral chordoma. Current trials continue these efforts and compare the different radiotherapies and determine appropriate doses. Research on radiation sensitizers for chordomas shows various therapies, ranging from hyperthermia to pharmaceutical options, that require further study. Full article

Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cellular signaling in cancer. Their functions are primarily mediated through interactions with specific protein partners that modulate chromatin structure, epigenetic remodeling, transcription, and signal transduction. In this review, we explore reports and strategies for the proteomic characterization of lncRNA-associated proteins, particularly emphasizing high-throughput liquid chromatography–mass spectrometry (LC-MS)-based techniques. Affinity-based methods such as RNA pull-down, ChIRP MS, RAP-MS, BioID-MS, and SILAC-MS enable sensitive and specific mapping of lncRNA and protein complexes. These approaches reveal cancer-specific proteomic signatures, post-translational modifications, and mechanistic insights into tumor biology. The use of label-free quantification, bituminization, and crosslinking strategies further enhances the resolution of dynamic RNA–protein networks. Validation tools following bioinformatic analyses, such as Western blotting, immunohistochemistry, immunofluorescence, and ELISA, are used to prioritize and confirm findings. Candidate biomarkers from hepatocellular carcinoma to colorectal and prostate cancers, profiling lncRNA-associated proteins, hold promise for identifying clinically actionable biomarkers and therapeutic targets. This review highlights the translational relevance of lncRNA protein studies and advocates for their broader adoption in oncological research. In LC-MS workflows, proteins bound to lncRNAs are enzymatically digested into peptides, separated via nano-LC, and analyzed using high-resolution tandem MS. Label-free or isotope-labeled methods quantify differential enrichment, followed by bioinformatics-driven pathway annotation. Full article

Bone loss is common in patients affected by pituitary and neuroendocrine disorders as both hormone excess and hormone deficiency can affect bone structure. There is increasing evidence that pituitary hormones directly influence bone cells turnover by bypassing endocrine organs. Osteopenia, osteoporosis, and vertebral fractures often result from these skeletal changes; however, diagnosing and managing bone frailty in pituitary and neuroendocrine disorders is still challenging because of the unpredictable outcomes in terms of fracture risk, even after the improvement of pituitary dysfunction, and the limited evidence for the use of bone-active drugs in these pathologies. The use of vitamin D supplements for fracture prevention is still debated in these secondary forms of bone frailty, although some studies have shown similar benefits to those derived in the general population. This review offers an overview on the characteristics of bone fragility in different pituitary and neuroendocrine diseases, and focuses on the prevention and treatment of skeletal disorders with bone-active drugs and vitamin D formulations currently available in this setting. Full article

The invention of antibacterial agents (antibiotics) was a significant event in the history of the human race, and this invention changed the way in which infectious diseases were cured; as a result, many lives have been saved. Recently, antibiotic resistance has developed as a result of excessive use of antibiotics, and it has become a major threat to world health. ARGs are spread across biomes and taxa of bacteria via lateral or horizontal gene transfer (HGT), especially via conjugation, transformation, and transduction. This review concerns transduction, whereby bacteriophages or phages facilitate gene transfer in bacteria. Bacteriophages are just as common and many times more numerous than their bacterial prey, and these phages are much more influential in controlling the population of bacteria. It is estimated that 25% of overall genes of Escherichia coli have been copied by other species of bacteria due to the HGT process. Transduction may take place via a generalized or specialized mechanism, with phages being ubiquitous in nature. Phage and virus-like particle (VLP) metagenomics have uncovered the emergence of ARGs and mobile genetic elements (MGEs) of bacterial origins. These genes, when transferred to bacteria through transduction, confer resistance to antibiotics. ARGs are spread through phage-based transduction between the environment and bacteria related to people or animals, and it is vital that we further understand and tackle this mechanism in order to combat antimicrobial resistance. Full article

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach. Full article

Taken together, cardiovascular diseases (CVDs) have become one of the prime causes of the global disease burden. Aging is closely related to CVDs and is considered to be one of the crucial factors in the incidence of CVDs. In the process of aging, cellular senescence is an important cause of CVDs such as atherosclerosis and atrial fibrillation. The treatment for CVDs by targeting senescent cells has been carried out in cellular models, animal experiments, and anti-aging clinical trials. Chemical approaches to regulate the fate of senescent cells by senolytics and senomorphics, which could selectively eliminate senescent cells or inhibit their senescence-associated secretory phenotype (SASP) secretion, have been increasingly explored. Importantly, many natural products with promising biological activity extracted from food or medicine–food homology have the above-mentioned effects. Furthermore, the identification of the target cells or target proteins of these natural products is of great significance for the indication of their mechanism of action, and it also lays a scientific foundation for the realization of precision nutrition intervention in the future. This review details how senescent cells affect CVDs, how natural products target senescent cells through nutritional intervention, and research methods for natural products in cardiovascular aging. Full article