Pancreatic cancer is one of the leading causes of cancer-related death worldwide. This is due to delayed diagnosis and resistance to traditional chemotherapy. Delayed diagnosis is often due to the broad range of non-specific symptoms that are associated with the disease. Resistance to current chemotherapies, such as gemcitabine, develops due to genetic mutations that are either intrinsic or acquired. This has resulted in poor patient prognosis and, therefore, justifies the requirement for new targeted therapies. A synthetic lethality approach, that targets specific loss-of-function mutations in cancer cells, has shown great potential in pancreatic ductal adenocarcinoma (PDAC). Immunotherapies have also yielded promising results in the development of new treatment options, with several currently undergoing clinical trials. The utilisation of monoclonal antibodies, immune checkpoint inhibitors, adoptive cell transfer, and vaccines have shown success in several neoplasms such as breast cancer and B-cell malignancies and, therefore, could hold the same potential in PDAC treatment. These therapeutic strategies could have the potential to be at the forefront of pancreatic cancer therapy in the future. This review focuses on currently approved therapies for PDAC, the challenges associated with them, and future directions of therapy including synthetically lethal approaches, immunotherapy, and current clinical trials.
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http://dx.doi.org/10.3390/cancers14102417 | DOI Listing |
J Magn Reson Imaging
January 2025
Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
Pancreatic ductal adenocarcinoma (PDAC) is the deadliest malignant tumor, with a grim 5-year overall survival rate of about 12%. As its incidence and mortality rates rise, it is likely to become the second-leading cause of cancer-related death. The radiological assessment determined the stage and management of PDAC.
View Article and Find Full Text PDFTher Adv Med Oncol
January 2025
Centro Integral Oncológico Clara Campal HM CIOCC, Hospital Universitario HM Sanchinarro, Madrid, Spain.
Treatment with pegylated nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (folinic acid; 5-FU/LV) has demonstrated remarkable efficacy for metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical trials. However, real-world data on the effectiveness of nal-IRI+5-FU/LV is heterogeneous and is lacking in Spain. To assess the effectiveness and safety of nal-IRI+5-FU/LV in real-life PDAC patients in Spain.
View Article and Find Full Text PDFExp Mol Med
January 2025
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
Most cancer mutation profiling studies are laboratory-based and lack direct clinical application. For clinical use, it is necessary to focus on key genes and integrate them with relevant clinical variables. We aimed to evaluate the prognostic value of the dosage of the KRAS G12 mutation, a key pancreatic ductal adenocarcinoma (PDAC) variant and to investigate the biological mechanism of the prognosis associated with the dosage of the KRAS G12 mutation.
View Article and Find Full Text PDFLife Sci
January 2025
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University, Sector-125, Noida 201313, Uttar Pradesh, India. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and grave malignancies with confined and ineffective therapeutic options. XPO1 is a critical regulator of nuclear export and activation of tumor suppressor proteins. The present study evaluated the therapeutic potential and molecular mechanisms of XPO1 inhibition against PDAC.
View Article and Find Full Text PDFJAMA Netw Open
January 2025
Huntsman Cancer Institute, University of Utah Health Care, Salt Lake City.
Importance: Despite the high prevalence of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC), the clinical impact of common KRAS mutations with different cytotoxic regimens is unknown. This evidence is important to inform current treatment and provide a benchmark for emergent targeted KRAS therapies in metastatic PDAC.
Objective: To assess the clinical implications of common KRAS G12 mutations in PDAC and to compare outcomes of standard-of-care multiagent therapies across these common mutations.
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