Pancreatic cancer is a disease with no effective treatment. Itâs low five-year survival rate, estimated at between 6% and 7.7%, ranks it the fourth highest of cancer-related of death in the U.S. despite being the twelfth most common type of cancer. Each year in the U.S., there are nearly 50,000 new cases and more than 40,000 deaths caused by the disease. By 2030, pancreatic cancer is expected to be the second most common cancer-related cause of death in the U.S. Resistance of pancreatic cancer to current treatment regimens (both surgery and chemotherapy) contributes to the dismal prognosis of this malignancy. The current standard of care for pancreatic cancer is chemotherapy, namely gemcitabine, Abraxane and the Folfirinox regimens. Less than 25% of patients respond after enduring treatment 3.4 months of treatment costing $118,000. The price is high given the poor outcome: Disease progression is delayed an average of 5.5 months and death by 8.5 months. During the past decade, more than 20 phase II/III clinical trials sought out cures for pancreatic cancer, and none was successful. Todayâs most effective regimens carry significant toxicities and offer marginal durable efficacy. Thus, there is a clear and unmet need for significant improvements in pancreatic cancer therapy. To this end, Avenzoar has developed a novel new chemical entity, AP-001, that interacts simultaneously with two proteins that are highly activated in pancreatic adenocarcinoma (PDAC): Glycogen synthase kinase 3 beta (GSK-3β) and histone deacetylase (HDAC). This Phase I project will establish dosage levels of AP-001 for animal studies, and then test the combination of AP-001 with standard treatments in a mouse model of pancreatic adenocarcinoma (PDAC) to determine relative efficacy as a key step to inform clinical trial design.
Public Health Relevance Statement: Project Narrative Pancreatic cancer is one of the deadliest forms of cancer, with 80% of patients dying within a year and as few as 7% of patients surviving for five years. AP-001 is a novel compound with low toxicity that has the potential to augment the limited efficacy of current treatment regimens by inhibiting metastasis and chemo-resistance signaling pathways, while reversing the disorders of immune regulation caused by the cancer. Its development could significantly improve prognosis and fill the critical need for effective pancreatic cancer therapy.
Project Terms: Abraxane; Animal Model; Animals; anti-cancer; Apoptosis; base; Biodistribution; cancer cell; Cancer Etiology; cancer therapy; cancer type; Cause of Death; cell motility; Cell Survival; Cessation of life; Chemicals; chemotherapy; Clinical Trials; Clinical Trials Design; Control Groups; Data; design; Development; Diagnosis; Disease; Disease Outcome; Disease Progression; dosage; Drug Combinations; Drug Kinetics; drug testing; effective therapy; efficacy study; epithelial to mesenchymal transition; Exhibits; experimental study; falls; gemcitabine; glycogen synthase kinase 3 beta; glycogen synthase kinase 3 beta inhibitor; HDAC1 gene; Histone Deacetylase; Histone Deacetylase Inhibitor; Histone Deacetylation; Human; Immune System Diseases; immunoregulation; improved; Incidence; interest; intravenous administration; irradiation; Malignant neoplasm of pancreas; Malignant Neoplasms; Maximum Tolerated Dose; Mediating; Metastatic Neoplasm to the Liver; model design; mortality; mouse model; Mus; Neoplasm Metastasis; novel; Operative Surgical Procedures; Organ; outcome forecast; Pancreas; Pancreatic Adenocarcinoma; pancreatic cancer cells; pancreatic cancer model; pancreatic cancer patients; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; prevent; Price; Probability; Proteins; Publishing; Regimen; Resistance; Side; Signal Pathway; standard care; standard of care; stemness; Survival Rate; targeted treatment; Testing; Therapeutic; Tissue Sample; Toxic effect; transcription factor; Treatment Cost; treatment effect; Treatment Protocols; tumor; tumor microenviron
