New advances in basic research, clinical diagnosis and treatment of pancreatic cancer in 2024

Pancreatic cancer is a highly malignant tumor, and its incidence rate has been slowly increasing since 2000. Although the improvement of diagnosis and treatment has led to an increase in the five-year survival rate of pancreatic cancer compared to 50 years ago, it remains one of the discouraging tumor diseases regarding its prognosis. In 2024, many achievements were made in the research of early screening, disease mechanism, clinical diagnosis and treatment of pancreatic cancer, showing a good prospect for clinical application. In early screening, artificial intelligence (AI) technology has empowered early diagnosis and screening of pancreatic cancer, pushing clinical diagnosis and treatment to a new level. Additionally, improvements in the accuracy of technologies such as liquid biopsy have provided new directions for early screening of pancreatic cancer. In terms of research on disease pathogenesis, 3D genome mapping technology has revealed the polyclonal origin and genetic heterogeneity of pancreatic intraepithelial neoplasm (PanIN). In basic research, a branched organ simulation system that mimics the unique structural characteristics of pancreatic cancer provides a new model for in vitro studies of pancreatic cancer. Lactate, an important tumor metabolite, links the metabolic microenvironment of pancreatic cancer with epigenetic changes, revealing potential therapeutic targets. Defects in the histone H3K36 trimethyltransferase SETD2 contribute to endogenous epigenetic dysregulation in pancreatic cancer and promote mitochondrial oxidative phosphorylation (OXPHOS) and tumor progression. The platelet-derived growth factor receptor (PDGFR) axis, which facilitates communication between stromal cells and cancer cells, forms a bidirectional secretory circuit and may become a new therapeutic target. Chimeric antigen receptor macrophage (CAR-M) therapy targeting the tyrosine kinase receptor c-MET demonstrates potential for synergistic enhancement with chemotherapy drugs. Macrophages in the pancreatic cancer microenvironment promote the development of pancreatic cancer cachexia through the CCL5/TRAF6/nuclear factor-κB (NF-κB) pathway, suggesting that macrophages could be an effective target for predicting and intervening in the development of pancreatic cancer cachexia. In terms of advancements in diagnosis and treatment, surgery following neoadjuvant chemotherapy can improve overall survival (OS) in resectable and borderline resectable patients, but further optimization of neoadjuvant chemotherapy protocols is needed. The first clinically effective KRASG12D-targeted drug has been reported, and research on inhibitors of a wide range of KRAS mutants is continually emerging. Patient stratification based on glycolysis-related scores (GRS) can further guide the selection of treatment protocols. “Intelligent exosomes” (ExoSmart) enhance cellular uptake capacity to assist in improving chemotherapy efficacy. The implementation of clinical trials combining immunotherapy with chemotherapy is expected to synergistically improve the efficacy of pancreatic cancer treatment. Pembrolizumab and anlotinib combined with albumin-bound paclitaxel/gemcitabine (PAAG) have shown great efficacy and safety in first-line treatment of metastatic pancreatic cancer (mPC) patients. The cancer vaccine ELI-002 2P, which targets KRAS mutation-encoded neoantigens, can induce an antitumor immune response. Oncolytic adenovirus therapy can synergistically improve the efficacy of treatment in advanced pancreatic ductal adenocarcinoma patients when combined with chemotherapy. This article reviewed the latest major progress in the field of basic research and diagnosis and treatment of pancreatic cancer in 2024.