A personalized mRNA vaccine has exhibited potential in the treatment of pancreatic cancer

Pancreatic cancer (PaCa) is a lethal cancer with an increasing incidence, highlighting the need for early prevention strategies. There is a lack of a comprehensive PaCa predictive model derived from large prospective cohorts. Therefore, we have developed an integrated PaCa risk prediction model for PaCa using data from the UK Biobank, incorporating lifestyle-related, genetic-related, and medical history-related variables for application in healthcare settings. We used a machine learning-based random forest approach and a traditional multivariable logistic regression method to develop a PaCa predictive model for different purposes. Additionally, we employed dynamic nomograms to visualize the probability of PaCa risk in the prediction model. The top five influential features in the random forest model were age, PRS, pancreatitis, DM, and smoking. The significant risk variables in the logistic regression model included male gender (OR = 1.17), age (OR = 1.10), non-O blood type (OR = 1.29), higher polygenic score (PRS) (Q5 vs. Q1, OR = 2.03), smoking (OR = 1.82), alcohol consumption (OR = 1.27), pancreatitis (OR = 3.99), diabetes (DM) (OR = 2.57), and gallbladder-related disease (OR = 2.07). The area under the receiver operating curve (AUC) of the logistic regression model is 0.78. Internal validation and calibration performed well in both models. Our integrative PaCa risk prediction model with the PRS effectively stratifies individuals at future risk of PaCa, aiding targeted prevention efforts and supporting community-based cancer prevention initiatives.

Efficient and targeted delivery of a DNA payload is vital for developing safe gene therapy. Owing to the recent success of commercial oncolytic vector and multiple COVID-19 vaccines, adenovirus vectors are back in the spotlight. Adenovirus vectors can be used in gene therapy by altering the wild-type virus and making it replication-defective; specific viral genes can be removed and replaced with a segment that holds a therapeutic gene, and this vector can be used as delivery vehicle for tissue specific gene delivery. Modified conditionally replicative–oncolytic adenoviruses target tumors exclusively and have been studied in clinical trials extensively. This comprehensive review seeks to offer a summary of adenovirus vectors, exploring their characteristics, genetic enhancements, and diverse applications in clinical and preclinical settings. A significant emphasis is placed on their crucial role in advancing cancer therapy and the latest breakthroughs in vaccine clinical trials for various diseases. Additionally, we tackle current challenges and future avenues for optimizing adenovirus vectors, promising to open new frontiers in the fields of cell and gene therapies.

Orodispersible films (ODFs) are thin, mechanically strong, and flexible polymeric films that are designed to dissolve or disintegrate rapidly in the oral cavity for local and/or systemic drug delivery. This review examines various aspects of ODFs and their potential as a drug delivery system. Recent advancements, including the detailed exploration of formulation components, such as polymers and plasticizers, are briefed. The review highlights the versatility of preparation methods, particularly the solvent-casting production process, and novel 3D printing techniques that bring inherent flexibility. Three-dimensional printing technology not only diversifies active compounds but also enables a multilayer approach, effectively segregating incompatible drugs. The integration of nanoparticles into ODF formulations marks a significant breakthrough, thus enhancing the efficiency of oral drug delivery and broadening the scope of the drugs amenable to this route. This review also sheds light on the diverse in vitro evaluation methods utilized to characterize ODFs, ongoing clinical trials, approved marketed products, and recent patents, providing a comprehensive outlook of the evolving landscape of orodispersible drug delivery. Current patient-centric approaches involve developing ODFs with patient-friendly attributes, such as improved taste masking, ease of administration, and enhanced patient compliance, along with the personalization of ODF formulations to meet individual patient needs. Investigating novel functional excipients with the potential to enhance the permeation of high-molecular-weight polar drugs, fragile proteins, and oligonucleotides is crucial for rapid progress in the advancing domain of orodispersible drug delivery.