Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic cancer has become the third most deadly cancer in America, with a steadily increasing rate of incidence. Here at Protheragen, we strive to support scientists and researchers in combating pancreatic ductal adenocarcinoma (PDAC) with our all-inclusive, one-stop services spanning from diagnostics and therapeutics to disease modeling and preclinical research. We focus on the unique link between PDAC and iron metabolism.
Overview of Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic ductal adenocarcinoma (PDAC) is considered to be one of the most aggressive solid tumors, making up roughly 90% of pancreatic cancers. Although relatively rare, it is the fourth most common cause of cancer mortality in the world today, which is primarily due to late stage of disease detection. PDAC is characterized by recurrent mutations in four cancer genes, including KRAS, CDKN2A, SMAD4, and TP53.
Fig.1 New strategies to target oxidants for PDAC therapy. (Lopez-Blazquez, C., et al., 2023)
Iron Metabolism Abnormalities in Pancreatic Ductal Adenocarcinoma (PDAC)
PDAC displays considerable disruption of iron metabolism owing to the aberrant regulation of iron-bioactive molecules, which contributes to tumor growth. The hepcidin-regulating gene pathway is notably implicated in PDAC, in which HJV, HAMP, TFR1, TFR2, and BMP6 show the strongest contribution. Furthermore, increased ferritin concentration is directly associated with the aggressiveness of PDAC and worsened outcomes. Modulating PDAC growth and chemoresistance through therapeutic intervention on iron metabolism illustrates its importance in tumor biology.
Fig.2 Ferroptosis mechanisms in PDAC. (Li, C., et al., 2022)
Therapeutics Development for Pancreatic Ductal Adenocarcinoma (PDAC)
| Drug Name | Mechanism of Action | Targets | Research Phase |
| Artesunate | Engage different PDAC cell lines to induce iron-triggered and ROS-mediated cell death. | ATP2A1, SERCA2 | Preclinical |
| Laminarin | In pancreatic cancer cells, it reduces ROS-mediated cellular migration and invasiveness due to mitochondrial dysfunction. | ROS | Preclinical |
| RSL-3 | Utilize anti-angiogenesis and trigger ferroptosis to obstruct the progression of pancreatic cancer. | GPX4 | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.
Our Services
Protheragen utilizes our knowledge of iron metabolism and our vast experience in oncology to provide an integrated suite of services designed to expedite your PDAC research and therapy development pipeline. We provide comprehensive services for the creation of innovative PDAC therapies, from target identification to preclinical validation, through the provision of comprehensive multi-dimensional services in diagnostics and therapeutics, disease modeling, as well as pharmacokinetics and safety evaluation of the drugs.
Therapeutic Development Services
- Small Molecule Drug Development
- Cell Therapy Development
- Gene Therapy Development
- Therapeutic Antibody Development
- Therapeutic Peptide Development
- Therapeutic Protein Development
Animal Model Development Services for PDAC
Animal models are, without a doubt, key instruments for PDAC research because they help in deciphering disease mechanisms, novel therapeutic targets, and in the rigorous testing of therapeutic and safety protocols. We offer customized services to develop and utilize advanced animal models to examine the precise effects of iron dysregulation on the initiation and progression of PDAC and to test the efficacy of iron-targeted therapies.
Genetically engineered models involve particular genes altered in animals that develop tumors simulating human PDAC.
- KC model (KrasLSL.G12D/+; Pdx-1-Cre)
- KPC model (KrasLSL.G12D/+; p53R172H/+; Pdx-1-Cre)
Xenograft models are created by implanting human tumors or cell lines into immune-compromised mice.
Pharmacokinetics and Drug Safety Evaluation Services
At Protheragen, we focus on improving the understanding and therapy of PDAC with an emphasis on iron metabolism. Collaborate with us so we can help you translate your research into novel therapeutics for cancer individuals. Reach out today so we can discuss how our comprehensive services can enhance your PDAC research.
References
- Julián-Serrano, Sachelly, et al. "Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies." The American journal of clinical nutrition 114.4 (2021): 1408-1417.
- Lopez-Blazquez, Carlos, et al. "Iron-Dependent Cell Death: A New Treatment Approach against Pancreatic Ductal Adenocarcinoma." International journal of molecular sciences 24.19 (2023): 14979.
- Li, Chang, et al. "Emerging Potential Mechanism and Therapeutic Target of Ferroptosis in PDAC: A Promising Future." International journal of molecular sciences 23.23 (2022): 15031.