Pancreatic Acinar Carcinoma Research Articles

A patient with pancreatic acinar carcinoma a - a rare clinical case report

A patient with pancreatic acinar carcinoma a - a rare clinical case report

Genomic classifier aligns most pancreatic acinar carcinoma with pancreatic ductal adenocarcinoma

Genomic classifier aligns most pancreatic acinar carcinoma with pancreatic ductal adenocarcinoma

A novel GLCC1::BRAF fusion with independent MYCN and MYC amplifications in primary tumor and metastasis in pediatric pancreatic acinar carcinoma

Abstract Introduction/Objective Pediatric pancreatic acinar cell carcinoma (PACC) is a rare malignancy, comprising 5-15% of pediatric pancreatic tumors. BRAF rearrangement is found in 20-30% of PACC cases, most commonly an inversion in chromosome 7. We report a case of PACC with GLCC1::BRAF fusion. Methods/Case Report A 10-year-old male presented with six months of weight loss, back pain, and loose stools. Imaging demonstrated concentric soft tissue thickening around the celiac axis and superior mesenteric artery, clinically interpreted as vasculitis. Follow-up imaging showed extension of the soft tissue thickening, prompting biopsy of a periaortic lymph node showing metastatic PACC. Pancreaticduodenectomy revealed a 3.8 cm pancreatic neck mass with perineural invasion and metastatic deposits in multiple lymph nodes and retroperitoneal soft tissue. Fluorescence in situ hybridization of both specimens demonstrated BRAF gene rearrangement, with the partner identified as GLCC1 by next generation sequencing and fusion assays. Microarray on the lymph node demonstrated amplification of MYC on chromosome 8, but not in the resection specimen, which showed gain of chromosome 2 and amplification of MYCN. Results (if a Case Study enter NA) NA Conclusion The GLCC1::BRAF fusion has previously been reported once in a case of pheochromocytoma with peritoneal seeding. The MYC gene family members, c-MYC and MYCN, are involved many cancer types; amplifications are often associated with unfavorable prognosis in tumors such as neuroblastoma. However, the amplification of both genes in the same tumor at different loci has not been reported. The combination of the primary GLCC1::BRAF fusion with secondary amplification of MYC and MYCN is likely to drive the aggressive behavior and metastasis in this case of PACC. Treatment for PACC includes chemoradiation and BRAF inhibition. However, BRAF rearrangements without the V600E mutation show variable response to BRAF inhibitors. Potential alternatives include inhibitors to other targets within the BRAF signaling pathway. Further investigation is needed to determine the clinicopathologic impact of these novel genetic aberrancies.

Ulcerated, tender nodules of the lower extremities

Ulcerated, tender nodules of the lower extremities

Relevance of detection of RAF fusion in pan-negative melanoma in routine practice.

e21500 Background: Pan-negative melanomas (i.e. without MAPK kinase pathway alteration and C-kit wild type) account for 30% of melanomas (according to the AACR GENIE database). In case of immunotherapy failure, therapeutic options are limited. Oncogene fusions represent a target of interest in many solid cancers (NSCLC, Cholangiocarcinoma, Glioma, GIST, pancreatic acinar carcinoma, thyroid, and prostate cancers). In melanoma, the frequency of oncogene fusion is not well documented and not routinely investigated. Methods: We conducted a single-center retrospective study. The objective was to determine the frequency of oncogene fusion detected by RNA sequencing (Archer Fusion pLex) performed in routine practice, in patients with advanced or metastatic pan negative melanoma. Data on clinical, pathological, and molecular characteristics and patient outcomes were collected. Analysis was carried out on the genetic material available for the diagnosis of the disease except for 1 patient who benefited from a new anatomopathological sample during an unfavorable evolution. In parallel, an extended molecular alteration search was performed using extended targeted NGS (OncoMine Comprehensive Assay panel). Results: We identified 48 patients with an advanced pan negative melanoma between January 2021 and January 2022 with a median age at diagnosis of 63 years. It was a cutaneous melanoma in 72,9 % (35/48) of the cases, a mucous melanoma in 14,5% (7/48) of the cases and a melanoma of unknown primary site in 12,5% (6/48) of the cases. The detection of fusion transcript was made in 89,5 % (43/48) of the cases. We identified 6 patients with a RAF fusion, including 4 BRAF gene fusion (MKLN1-BRAF, AGK-BRAF, SNX29-BRAF, PTPRJ-BRAF) and 2 RAF1 fusion (MAP4-RAF1, EFCC1-RAF1). Of the other molecular alterations, NF1 mutation was the most frequent molecular alteration identified (25 % (12/48) of patients). At lower frequencies, 6,8 % (3/48) of patients had a PI3K mutation, and 8,3 % (4/48) of patients had NOTCH, PTCH1, GNAQ mutations. Among the 6 patients with RAF fusions, all the patients initially received treatment with anti-PD1+/- anti-CTLA4 immunotherapy. After immunotherapy failure, 4 patients benefited from second-line targeted therapy (2 with BRAF and MEK inhibitors combination, 2 MEK inhibitors alone). One patient presented an objective imaging response, the other three patients have not yet benefited from reassessment imaging. Conclusions: In a population of pan negative melanoma, we detected 12,5 % (6/48) of RAF fusion. Fusion detection allowed the introduction of a second line of targeted therapy, in the absence of a validated therapeutic option in 66,6 % (4/6) of cases This study suggests the relevance of detecting RAF fusion in a selected population.

Survival after Pancreatic Resection in Older Patients with Pancreatic Malignancy

Introduction: Pancreatic malignancies have among the highest mortality rates of solid organ cancers, and there has been a global trend towards an increasing incidence. In the context of an aging population, more older patients will present for consideration of curative resection. Although mortality and morbidity associated with pancreatic resection has improved, there are mixed outcomes reported in the literature regarding survival outcomes for older patients undergoing pancreatectomy. Methods: A retrospective cohort study was performed including patients ≥75 years of age undergoing pancreatic resection for primary pancreatic malignancy, identified using a prospectively maintained database of a single surgeon’s experience. The primary outcomes were median survival and 5-year overall survival. Secondary outcomes included hospital length of stay, peri-operative morbidity and mortality, patterns of recurrence and disease-free survival. Results: 41 patients aged ≥75 years were identified from a total of 497 major pancreatic resections for malignancy between 2007 and 2020. The mean age was 80.6 (range 75 - 88) Of these patients, patients underwent pancreacitoduodectomy (n=36), distal pancreatectomy (n=3), total pancreatectomy (n=2) for pancreatic adenocarcinoma (n=34), ampullary adenocarcinoma (n=5), pancreatic acinar carcinoma (n=1) and invasive microcystic cystadenoma (n=1). 21 patients (51%) had concurrent major vascular resection. The median survival was 24 months, and the 5-year overall survival rate 37%. 30-day and 90-day mortality was 0% and 4.9% (n=2), respectively. Conclusion: Pancreatic resection for malignancy in appropriately selected older adults is safe and confers comparable survival outcomes to the general population. Age alone should not be a contraindication to pancreatectomy.

Exome Sequencing of Pancreatic Acinar Carcinoma Identified Distinctive Mutation Patterns.

Pancreatic acinar cell carcinoma (ACC) is a rare pancreatic cancer. The advancement of treatment is hampered because of the limited knowledge of its molecular mechanism. Whole-exome sequencing was performed on DNA extracted from 11 pure ACC surgical samples. Potential germline variants were removed on the basis of polymorphic databases, alternative allele frequency, coverage depth, and Catalogue of Somatic Mutations in Cancer (COSMIC) annotations after variant calling procedure. Mutation profiles and signatures were assessed through the Mutational Patterns package. A median of 34 somatic mutations were detected (range, 19-60). Three novel recurrent small deletions were identified. Common pancreatic ductal adenocarcinoma mutations or neuroendocrine tumor mutants were not found. FAT atypical cadherin 4, mucin 5B, titin, and zinc finger homeobox 3 were consistently mutated across 4 independent ACC studies. A high contribution of COSMIC mutational signature 1 was seen in ACC, indicating deamination of 5-methylcytosine. The majority of the patients had COSMIC signatures 6, 15, or 20, relating to defective DNA mismatch repair. Six patients showed COSMIC mutational signature 10 because of the altered activity of DNA polymerase epsilon. Distinct mutational signatures pathways were found in ACC and targeting them may improve clinical outcome.

Abstract 817: Pancreatic acinar carcinoma - a rare entity with a targetable BRAF V600E mutation

Abstract Background: Pancreatic acinar carcinomas account for less than 1% of all pancreatic cancers and are considered genetically distinct entities form other pancreatic carcinomas. The pathogenesis of this malignancy is incompletely understood, and the efficacy of cytotoxic chemotherapy is not well defined especially in unresectable or metastatic disease. Methods: We identified one patient with pancreatic acinar carcinoma who was treated at our institution and was found to have a unique targetable pathogenic mutation on tumor sequencing. Results: A 64-year-old male patient was diagnosed with localized pancreatic acinar carcinoma during workup for epigastric pain. He underwent distal pancreatectomy with final pathology consistent with stage T3N0 acinar cell carcinoma without any adenocarcinoma component. He subsequently received six months of adjuvant chemotherapy with gemcitabine plus capecitabine, derived from evidence on pancreatic adenocarcinoma due to the size of his original tumor. Seven months after completion of adjuvant therapy, he was found to have local recurrence within the surgical bed and was treated with three cycles of systemic chemotherapy with FOLFIRINOX. During a following planned surgical resection, multiple liver lesions were seen intraoperatively, and surgery was aborted. Liver lesions were biopsied and hybrid capture next-generation sequencing was performed which revealed: a BRAF V600E gain of function mutation, CDKN2A loss as well as MYCN amplification. The patient declined further chemotherapy and his treatment was switched to Encorafenib (BRAF inhibitor) plus Binimetinib (MEK inhibitor). He attained a partial response to therapy at his first restaging CT scan after 2 months of therapy (-39% per RECIST 1.1). Both mass at the surgical bed as well as liver metastases were decreased in size. He tolerated treatment very well without significant adverse events (including no clinically significant rash). Conclusions: While BRAF rearrangements as described in the literature may occur in 15-23% of patients with acinar cell carcinoma of the pancreas, BRAF activating mutations and in particular the BRAF V600E substitution has not been reported. This particular substitution is commonly present in melanoma, hairy cell leukemia, Langerhans cell histiocytosis and less frequently in lung and colon cancer. A combination of BRAF and MEK inhibition may be used in patients with tumors harboring this activating mutation with variable efficacy across different histologies. In light of the rarity of acinar cell carcinomas of the pancreas and the lack of established systemic treatment guidelines, tumor sequencing should be considered if no other therapies are available. This is the first case reported in the literature of a patient with acinar cancer of the pancreas and BRAF V600E mutation where targeted therapy has shown an early response. Citation Format: Vaia Florou, Chris Nevala-Plagemann, Sean Mulvihill, Ignacio Garrido-Laguna. Pancreatic acinar carcinoma - a rare entity with a targetable BRAF V600E mutation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 817.

Histopathology and Feline Pancreatic Lipase Immunoreactivity in Inflammatory, Hyperplastic and Neoplastic Pancreatic Diseases in Cats

The most common pancreatic diseases in cats are pancreatitis and exocrine pancreatic insufficiency (EPI). Non-invasive methods, such as serological quantification of feline pancreatic lipase immunoreactivity (fPLI), are often used in the diagnosis of pancreatitis. Previous studies have compared fPLI concentrations with histopathology, considered to be the gold standard for diagnosis of feline pancreatitis. However, fPLI concentrations in cats suffering from pancreatic tumours were rarely described. The aim of the present study was to determine the sensitivity and specificity of an in-house enzyme-linked immunosorbent assay (ELISA) for the quantification of fPLI in serum samples based on histopathological findings in cats diagnosed with various pancreatic diseases. Pancreatic biopsy samples from 80 cats were included. Five groups were defined on the basis of pancreatic histopathology: group 1, normal pancreas; group 2, nodular hyperplasia; group 3, mild pancreatitis; group 4, marked (moderate/severe) pancreatitis; and group 5, pancreatic neoplasia. Serum samples from all cats were tested by fPLI ELISA (<3.6μg/l normal, 3.6-5.3μg/l questionable, >5.3μg/l pancreatitis). In group 1 (n=19), serum fPLI values were within the reference interval in 74% of cases and in group 2 (n=9) in 78%. Cats with mild pancreatitis (n=23), marked pancreatitis (n=11) and pancreatic neoplasms (n=18) had significantly increased fPLI concentrations compared with group 1 (P=0.004/0.001/≤0.0001). Cats with nodular hyperplasia had significantly lower fPLI values than cats with marked pancreatitis (P=0.048) or tumours (P=0.002). Serum fPLI concentrations in group 3 were <3.6μg/l (n=6), 3.6-5.3μg/l (n=4) and >5.3μg/l (n=13). Calculated test sensitivity for mild pancreatitis was fPLI >3.5μg/l: 73.9% and fPLI >5.3μg/l: 56.5%. In group 4 (n=11), seven of nine cats (77.8%) with marked purulent pancreatitis had elevated fPLI. In group 4, a sensitivity of 81.8% was detected for fPLI >3.5μg/l and 63.6% for fPLI >5.3μg/l. Two cats with marked non-purulent pancreatitis had elevated fPLI, while two cats with marked purulent pancreatitis had normal fPLI values (<3.6μg/l). In group 5, one cat with pancreatic adenoma and one with pancreatic acinar carcinoma had normal fPLI concentrations. The other cats with pancreatic adenoma (solid, n=1; cystic, n=4) or carcinoma (solid, n=9; cystic, n=2) had elevated or high fPLI values (4.1 to >40μg/l, median 21.2μg/l), probably caused by additional inflammation. The results of the present study confirm the importance of detailed histopathological characterization for the interpretation of clinical signs and fPLI values in feline pancreatitis. Primary pancreatic neoplasms may also lead to elevated fPLI concentrations as there is concurrent pancreatitis in most cases. However, severe pancreatic diseases, such as chronic non-purulent pancreatitis or tumours without inflammation, may result in normal fPLI values.

Lipase hypersecretion syndrome: A distinct form of paraneoplastic syndrome specific to pancreatic acinar carcinomas.

Lipase hypersecretion syndrome (LHS) is a paraneoplastic syndrome seen exclusively as a result of pancreatic acinar cell carcinoma (ACC). In LHS, acinar enzymes (lipase, trypsin and chymotrypsin) which are normally secreted to the duodenum for digestive purposes, are instead released to the blood by the carcinoma cells. In a way, it is "endocrine-ization" of an "exocrine" function. These circulating enzymes, especially lipase, exerts its digestive action on other tissues, especially on the subcutaneous tissues in the pressure poins of legs, creating a picture often mistaken as erythema nodosum or rheumatic nodules. The bone and joints may also be effected, which mostly appears to be secondary to the complications and super-infection of the skin lesions. Eosinophilia also often accompanies this syndrome. The accurate diagnosis of LHS requires the identification of the pancreatic primary as well as its correct classification as acinar because a variety of pancreatic tumors can be associated with skin lesions, ranging from rare metastasis of adenocarcinoma to the necrolytic migratory erythema caused by glucagon-producing neuroendocrine tumors. Towards this differential, the diagnostic characteristics of acinar cell carcinomas that have been better elucidated in the past decade often need to be employed in increasingly smaller specimens and the liver, especially since most LHS cases also have liver metastasis (presumably due to the by-pass of the "first-pass" liver metabolism phenomenon). ACC (and LHS) occur in patients in their 60's. The pancreatic mass is often large, round, demarcated and closely resemble neuroendocrine and solid-pseudopapillary neoplasms but are more atypical/proliferative, and commonly show single prominent nucleoli and a distinctive chromophilia. Immunostaining with trypsin/chymotrypsin, negativity of beta-catenin help in the differential; as a caveat, neuroendocrine differentiation is common in ACCs. In conclusion, LHS is a rare type of paraneoplastic syndrome specific to ACC. The accurate diagnosis requires attention to their subtle diagnostic characteristics.

Pancreatic acinar cells carcinoma in a female non-descript cat

The external examination of carcass of four year old female non-descript dead cat with history of ascites, anorexia, respiratory distress, dullness showed paler mucous membranes and approximately 650 ml of straw coloured fluid in the abdominal cavity. Microscopic examination of section of pancreatic tissue showed large sheets of poorly differentiated neoplastic cells with enlarged vesiculate nuclei and prominent nucleoli as pancreatic acinar cell carcinoma.

Prevention of pancreatic acinar cell carcinoma by Roux-en-Y Gastric Bypass Surgery

Roux-en-Y Gastric Bypass Surgery (RYGB) prevents the occurrence of pancreatic cell acinar carcinoma (ACC) in male and female Ngn3-Tsc1−/− mice. Ngn3 directed Cre deletion of Tsc1 gene induced the development of pancreatic ACC. The transgenic mice with sham surgery demonstrated a cancer incidence of 96.7 ± 3.35% and survival rate of 67.0 ± 1.4% at the age of 300 days. Metastasis to liver and kidney was observed in 69.7 ± 9.7% and 44.3 ± 8.01% of these animals, respectively. All animals with RYGB performed at the age of 16 weeks survived free of pancreatic ACC up to the age of 300 days. RYGB significantly attenuated the activation of mTORC1 signaling and inhibition of tumor suppressor genes: p21, p27, and p53 in pancreatic ACC. Our studies demonstrate that bariatric surgery may limit the occurrence and growth of pancreatic ACC through the suppression of mTORC1 signaling in pancreas. RYGB shows promise for intervention of both metabolic dysfunction and organ cancer.

Monoclonal Antibody Production Against Vimentin by Whole Cell Immunization in a Mouse Model.

BackgroundPancreatic carcinoma is the fourth-leading cause of cancer death in the United States and due to its late presentation, only few patients would be candidates for the curative treatment of pancreactomy. Monoclonal antibodies have brought hope to targeted therapy.ObjectivesTo identify new biomarkers, a panel of monoclonal antibodies was generated against newly established cell line, Faraz-ICR from a patient with pancreatic acinar cell carcinoma.Material and MethodsBalb/c female mice were immunized with Faraz-ICR cell line and their spleenocytes fused with SP2/0 myeloma cell line. Highly reactive hybridoma producing antibodies against Faraz-ICR was detected using ELISA, immunofluorescence staining and flow cytometry. Western blot and 2D immunoblot were utilized for further characterization of the target antibodies.ResultsAmong highly reactive clones, the reactivity of 7C11 clone was assessed in comparison to other epithelial tumors. The antibody isotype was IgM that reacted with a 55 kDa protein in western blot analysis. To further characterize the target antigen, immunoproteome of the Faraz-ICR cell line was performed. By LC-MS analysis, the target of 7C11 clone was identified to be vimentin.ConclusionsPancreatic cancer is a highly lethal malignancy with no reliable biomarker for early detection and diagnosis. In this study, by establishing a pancreatic acinar carcinoma cell line, a panel of monoclonal antibodies was generated to identify specific or associated cancer targets. Furthermore, 7C11 mAb was introduced that can specifically recognizes vimentin as a tumor marker. This antibody may serve as a new tool for prognostic and therapeutic strategies.

Diffuse involvement of pancreatic acinar cell carcinoma: a case report

Diffuse involvement of pancreatic acinar cell carcinoma: a case report

No Functional Role for microRNA-342 in a Mouse Model of Pancreatic Acinar Carcinoma.

The intronic microRNA (miR)-342 has been proposed as a potent tumor-suppressor gene. miR-342 is found to be downregulated or epigenetically silenced in multiple different tumor sites, and this loss of expression permits the upregulation of several key oncogenic pathways. In several different cell lines, lower miR-342 expression results in enhanced proliferation and metastasis potential, both in vitro and in xenogenic transplant conditions. Here, we sought to determine the function of miR-342 in an in vivo spontaneous cancer model, using the Ela1-TAg transgenic model of pancreatic acinar carcinoma. Through longitudinal magnetic resonance imaging monitoring of Ela1-TAg transgenic mice, either wild-type or knockout for miR-342, we found no role for miR-342 in the development, growth rate, or pathogenicity of pancreatic acinar carcinoma. These results indicate the importance of assessing miR function in the complex physiology of in vivo model systems and indicate that further functional testing of miR-342 is required before concluding it is a bona fide tumor-suppressor-miR.

MiR-29a-deficiency does not modify the course of murine pancreatic acinar carcinoma.

The development of cancers involves the complex dysregulation of multiple cellular processes. With key functions in simultaneous regulation of multiple pathways, microRNA (miR) are thought to have important roles in the oncogenic formation process. miR-29a is among the most abundantly expressed miR in the pancreas. Together with altered expression in pancreatic cancer cell lines and biopsies, and known oncogenic functions in leukemia, this expression data has identified miR-29a as a key candidate for miR involvement in pancreatic cancer biology. Here we used miR-29a-deficient mice and the TAg model of pancreatic acinar carcinoma to functionally test the role of miR-29a in vivo. We found no impact of miR-29a loss on the development or growth of pancreatic tumours, nor on the survival of tumour-bearing mice. These results suggest that, despite differential expression, miR-29a is oncogenically neutral in the pancreatic acinar carcinoma context. If these results are extended to other models of pancreatic cancer, they would reduce the attractiveness of miR-29a as a potential therapeutic target in pancreatic cancer.

No Effect of Dietary Aspartame or Stevia on Pancreatic Acinar Carcinoma Development, Growth, or Induced Mortality in a Murine Model.

Pancreatic cancer has an extremely poor prognosis, largely due to a poor record for early detection. Known risk factors for pancreatic cancer include obesity, diet, and diabetes, implicating glucose consumption and regulation as a key player. The role of artificial sweeteners may therefore be pertinent to disease kinetics. The oncogenic impact of artificial sweeteners is a highly controversial area. Aspartame, one of the most studied food additives, is widely recognized as being generally safe, although there are still specific areas where research is incomplete due to study limitations. Stevia, by contrast, has been the subject of relatively few studies, and the potential health benefits are based on extrapolation rather than direct testing. Here, we used longitudinal tracking of pancreatic acinar carcinoma development, growth, and lethality in a sensitized mouse model. Despite exposure to aspartame and stevia from the in utero stage onward, we found no disease modification activity, in either direction. These results contribute to the data on aspartame and stevia safety, while also reducing confidence in several of the purported health benefits.

CT and MRI features of pancreatic acinar cell carcinoma

Objective To identify the imaging features of pancreatic acinar cell carcinomas. Methods Eleven patients of pancreatic acinar cell carcinomas proven surgically and pathologically were included. We retrospectively evaluated the CT and MR findings including the location, size, shape, margin, necrosis , calcification, hemorrhage, enhancement degree, enhancement pattern, invasion to other organs, perilesional lymph nodes, metastasis, recurrence. Results The tumors were distributed in the head(n=4), body and tail(n=4),tail(n=3) of pancreas. The median tumor size was 97 mm(27 to 180 mm).Nine cases presented with a well-defined enhancing capsule. Tumor vessels could be seen in 9 cases.Seven cases were hypovascular while the other 4 were hypervascular. Different extents of necrosis could be seen in all masses as a swirling or cleft low density in the enhanced tumors, with an median of 10% (2% to 25%). The hypovascular masses more frequently demonstrated a lobulated tumor, heterogeneous enhancement pattern, with a larger necrotic component and were more common invasion to other organs. Conclusions Pancreatic acinar cell carcinoma typically presents as a sizable pancreatic mass with a well-defined enhancing capsule. Key words: Pancreatic neoplasms; Tomography, X-ray computed; Magnetic resonance imaging

Diagnosis and treatment analysis of 15 pancreatic acinar cell carcinoma patients

Diagnosis and treatment analysis of 15 pancreatic acinar cell carcinoma patients

Neurogenin 3–Directed Cre Deletion of Tsc1 Gene Causes Pancreatic Acinar Carcinoma

The role of tuberous sclerosis complex (TSC) in the pathogenesis of pancreatic cancers remains largely unknown. The present study shows that neurogenin 3 directed Cre deletion of Tsc1 gene induces the development of pancreatic acinar carcinoma. By cross-breeding the Neurog3-cre mice with Tsc1loxp/loxp mice, we generated the Neurog3-Tsc1−/− transgenic mice in which Tsc1 gene is deleted and mTOR signaling activated in the pancreatic progenitor cells. All Neurog3-Tsc1−/− mice developed notable adenocarcinoma-like lesions in pancreas starting from the age of 100days old. The tumor lesions are composed of cells with morphological and molecular resemblance to acinar cells. Metastasis of neoplasm to liver and lung was detected in 5% of animals. Inhibition of mTOR signaling by rapamycin significantly attenuated the growth of the neoplasm. Relapse of the neoplasm occurred within 14days upon cessation of rapamycin treatment. Our studies indicate that activation of mTOR signaling in the pancreatic progenitor cells may trigger the development of acinar carcinoma. Thus, mTOR may serve as a potential target for treatment of pancreatic acinar carcinoma.