Pancreatic Ductal Adenocarcinoma (PDAC) is the most common and deadliest form of pancreatic cancer. It is an extremely difficult-to-treat disease with a median survival of less than 1 year and a dismal 5-year survival rate of 3-5%. This is primarily due to a rapid dissemination of the tumors and a lack of effective biomarkers for early detection which means that in general, the cancer is fairly advanced when initially diagnosed. Currently, the chemotherapeutic drug gemcitabine is the first-line treatment for PDAC. However, gemcitabine does not significantly prolong survival and patients commonly develop chemoresistance and relapse. Thus, there is an urgent need for the identification of effective, new therapeutic strategies for the treatment of PDAC. BioTheryX is developing a novel chemotherapeutic that inhibits Wnt signaling and eukaryotic translation initiation factor 5A (eIF5A) activity for the treatment of pancreatic ductal adenocarcinoma (PDAC). Preliminary data suggest the compound is well tolerated in mice. The goal of this Phase I proposal is to demonstrate efficacy of this compound in an orthotopic PDAC animal model and advancing the compound to a Phase II for additional preclinical studies with the ultimate goal of filing an IND a the end of Phase II.
Public Health Relevance Statement: Public Health Relevance: The goal of this program is to develop and ultimately commercialize a novel small molecule drug for the treatment of pancreatic ductal adenocarcinoma (PDAC). PDAC is refractory to essentially all therapies to current treatments and has a media survival time of less than 1 year and a dismal 5 year survival rate of 3-5%.
NIH Spending Category: Cancer; Digestive Diseases; Orphan Drug; Pancreatic Cancer; Rare Diseases
Project Terms: Adenocarcinoma Cell; Agar; Amino Acids; Animal Model; Antifungal Agents; Biological Assay; Biological Availability; Biological Markers; Cancer cell line; cancer type; Cell Cycle; Cell model; Data; Development; Diagnosis; Disease; Dose; Drosophila genus; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Early Diagnosis; effective therapy; efficacy testing; Embryo; Enzymes; Eukaryotic Initiation Factors; FDA approved; Future; gemcitabine; Goals; Growth; hypusine; In Vitro; in vivo; Induction of Apoptosis; inhibitor/antagonist; Injectable; Iron; KRAS2 gene; Lead; Malignant neoplasm of pancreas; Malignant Neoplasms; Mixed Function Oxygenases; Modeling; mouse model; Mus; Mutation; Nature; Neoplasm Metastasis; novel; novel therapeutics; Oral; pancreatic cancer cells; Pancreatic Ductal Adenocarcinoma; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phosphotransferases; Post-Translational Protein Processing; pre-clinical; preclinical study; Prodrugs; programs; Proteins; Protocols documentation; Pseudopodia; public health relevance; Refractory; Regulation; Relapse; Resistance; Route; Safety; safety testing; Sampling; Schedule; Signal Pathway; Signal Transduction; Signaling Molecule; small molecule; Solid Neoplasm; Survival Rate; therapeutic target; Time; TimeLine; treatment strategy; tumor; Up-Regulation (Physiology)
