Emerging treatment approaches for triple-negative breast cancer.

Approximately, 15% of global breast cancer cases are diagnosed as triple-negative breast cancer (TNBC), identified as the most aggressive subtype due to the simultaneous absence of estrogen receptor, progesterone receptor, and HER2. This characteristic renders TNBC highly aggressive and challenging to treat, as it excludes the use of effective drugs such as hormone therapy and anti-HER2 agents. In this review, we explore standard therapies and recent emerging approaches for TNBC, including PARP inhibitors, immune checkpoint inhibitors, PI3K/AKT pathway inhibitors, and cytotoxin-conjugated antibodies. The mechanism of action of these drugs and their utilization in clinical practice is explained in a pragmatic and prospective manner, contextualized within the current landscape of standard therapies for this pathology. These advancements present a promising frontier for tailored interventions with the potential to significantly improve outcomes for TNBC patients. Interestingly, while TNBC poses a complex challenge, it also serves as a paradigm and an opportunity for translational research and innovative therapies in the field of oncology.

The Italian experience with the use of monitoring registers attached to negotiated agreements (MEAs) of the Italian Medicines Agency is a tool for governance and clinical appropriateness.

The use of monitoring registers with annexed negotiation agreements (MEAs) of the Italian Medicines Agency (AIFA) are the pillar of Italian healthcare governance to guarantee the correct allocation of economic healthcare resources. In Italy, an analysis was conducted in the context of a local health authority where all negotiation activities were implemented to verify the amount of reimbursements that can be recovered through the use of all available procedures on the monitoring registers. The purpose of this analysis was to highlight any criticalities which, if not properly addressed by doctors and pharmacists, can lead to considerable financial loss. Correct verification by the hospital pharmacy resulted in an economic recovery of approximately EUR 579,443.40 for the year 2022 and EUR 682,225.30 in the first 9 months of 2023. This analysis is intended to highlight how effective collaboration between doctors and pharmacists can lead to clear economic advantages with an efficient health system to the total benefit of citizens.

Beyond Body Size: Adiponectin as a Key Player in Obesity-Driven Cancers.

Obesity, a complex and multifactorial disease influenced by genetic, environmental, and psychological factors, has reached epidemic proportions globally, posing a significant health challenge. In addition to its established association with cardiovascular disease and type II diabetes, obesity has been implicated as a risk factor for various cancers. However, the precise biological mechanisms linking obesity and cancer remain largely understood. Adipose tissue, an active endocrine organ, produces numerous hormones and bioactive molecules known as adipokines, which play a crucial role in metabolism, immune responses, and systemic inflammation. Notably, adiponectin (APN), the principal adipocyte secretory protein, exhibits reduced expression levels in obesity. In this scoping review, we explore and discuss the role of APN in influencing cancer in common malignancies, including lung, breast, colorectal, prostate, gastric, and endometrial cancers. Our review aims to emphasize the critical significance of investigating this field, as it holds great potential for the development of innovative treatment strategies that specifically target obesity-related malignancies. Furthermore, the implementation of more rigorous and comprehensive prevention and treatment policies for obesity is imperative in order to effectively mitigate the risk of associated diseases, such as cancer.

Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology.

Cholangiocarcinoma (CCA) is a malignant neoplasm arising in the epithelium of the biliary tract. It represents the second most common primary liver cancer in the world, after hepatocellular carcinoma, and it constitutes 10-15% of hepatobiliary neoplasms and 3% of all gastrointestinal tumors. As in other types of cancers, recent studies have revealed genetic alterations underlying the establishment and progression of CCA. The most frequently involved genes are APC, ARID1A, AXIN1, BAP1, EGFR, FGFRs, IDH1/2, RAS, SMAD4, and TP53. Actionable targets include alterations of FGFRs, IDH1/2, BRAF, NTRK, and HER2. "Precision oncology" is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from "old" chemotherapies to "new" target-oriented drugs.

p53: From Fundamental Biology to Clinical Applications in Cancer.

p53 tumour suppressor gene is our major barrier against neoplastic transformation. It is involved in many cellular functions, including cell cycle arrest, senescence, DNA repair, apoptosis, autophagy, cell metabolism, ferroptosis, immune system regulation, generation of reactive oxygen species, mitochondrial function, global regulation of gene expression, miRNAs, etc. Its crucial importance is denounced by the high percentage of amino acid sequence identity between very different species (Homo sapiens, Drosophila melanogaster, Rattus norvegicus, Danio rerio, Canis lupus familiaris, Gekko japonicus). Many of its activities allowed life on Earth (e.g., repair from radiation-induced DNA damage) and directly contribute to its tumour suppressor function. In this review, we provide paramount information on p53, from its discovery, which is an interesting paradigm of science evolution, to potential clinical applications in anti-cancer treatment. The description of the fundamental biology of p53 is enriched by specific information on the structure and function of the protein as well by tumour/host evolutionistic perspectives of its role.