GrantZIABC
Rare Exocrine Tumors of the Pancreas
- Activity
- ZIA
- Institute
- BC
- Fiscal years
- 2021–2024
- Amount counted
- $939,401
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Abstract public domain (NIH RePORTER)
A) ASCP- Improving outcomes for patients with adenosquamous carcinoma of the pancreas (ASCP). ASCP is a highly aggressive variant of PDAC that consists of at least 30% squamous component on a background of typical glandular PDAC component. Aim1) Recent work by extramural collaborators (Von Hoff & Han) demonstrated that myc overexpression drives ASCP and that the small molecule drug Minnelide (Minneamrita Therapeutics LLC) is a superenhancer inhibitor that suppresses myc expression in ASCP. Based on these results, we have initiated a Phase 2 single-site, CCR-sponsored study to test the anti-tumor activity of Minnelide in patients with advanced, previously treated ASCP (PI Alewine). Correlative studies examining drug bioactivity, affect on immune components, and ASCP molecular fingerprint will be performed by collaborators with expertise in these areas. Completion of accrual is expected later in 2024. Aim2) Multiple researchers have shown transcriptional between the basal and classical subtypes of PDAC. Basal subtype is associated with a squamous phenotype and confers poor prognosis. By using forced expression of a squamous differentiation program in human pancreatic cancer cells, we have investigated whether these cells A) preferentially metastasize in mice and B) are enriched following chemotherapy treatment. B) PACC- Improving outcomes for patients with pancreatic acinar cell carcinoma (PACC). PACC is an ultra-rare tumor type that is histologically and genetically distinct from PDAC. Aim1: Investigate the Natural History of PACC. We have accrued >10 PACC patients to Rare Solid Tumor Natural History Study (PI: Wedekind-Malone) and are following these patients. Aim 2: Develop pre-clinical models of PACC. We have initiated a collaboration with CAPR Frederick (S. Kozlov) to engineer a PACC GEMM. Aim 3: Identify new treatments for PACC. We have initiated a Phase 2 trial to test olaparib in patients with PACC based on research by us and others suggesting that PACC is an ID3 deficient tumor and that deficiency of ID3 leads to PARP inhibitor sensitivity.