Extracellular vesicles (EVs) are secreted, cell-derived, membrane-bound compartments implicated in various diseases for their ability to influence distant targets and as carriers of biomarkers. Here, we present a protocol for separating EVs from mammalian pancreatic cancer cells and their characterization using western blot and electron microscopy. We then demonstrate how they are utilized to affect tumor development in a murine model of metastatic pancreatic cancer including a method to quantify hepatic tumor burden in histologic samples.For complete details on the use and execution of this protocol, please refer to Dudgeon et al.1

Summary The mechanisms that regulate cancer dormancy remain poorly understood. Using a mouse model of resectable pancreatic adenocarcinoma (PDAC), we identified Dec2 as a gene that was upregulated in metastatic dormant tumor cells. Deletion of Dec2 from tumor cells substantially increased mouse survival after resection due to an immune-mediated mechanism as the survival benefit was abrogated in immunodeficient conditions. Dec2 promoted immune evasion by repressing multiple components of the MHC-I dependent antigen presentation pathway in tumor cells. Dec2 is a regulator of circadian rhythms, and we found several components of the antigen presentation pathway oscillated in a circadian manner that was lost upon deletion of Dec2. Moreover, T-cell mediated tumor cell killing varied depending on the time of day. We suggest that lowered MHC-I presentation of antigens during rest phase is a natural effect of the circadian clock, which is exploited by Dec2-overexpressing pancreatic tumors to evade the immune system. ### Competing Interest Statement The authors have declared no competing interest.

The biology of metastatic pancreatic ductal adenocarcinoma (PDAC) is distinct from that of the primary tumor due to changes in cell plasticity governed by a distinct transcriptome. Therapeutic strategies that target this distinct biology are needed. We detect an upregulation of the neuronal axon guidance molecule Netrin-1 in PDAC liver metastases that signals through its dependence receptor (DR), uncoordinated-5b (Unc5b), to facilitate metastasis in vitro and in vivo. The mechanism of Netrin-1 induction involves a feedforward loop whereby Netrin-1 on the surface of PDAC-secreted extracellular vesicles prepares the metastatic niche by inducing hepatic stellate cell activation and retinoic acid secretion that in turn upregulates Netrin-1 in disseminated tumor cells via RAR/RXR and Elf3 signaling. While this mechanism promotes PDAC liver metastasis, it also identifies a therapeutic vulnerability, as it can be targeted using anti-Netrin-1 therapy to inhibit metastasis using the Unc5b DR cell death mechanism.

Latent recurrence following curative-intent pancreatic cancer surgery is a major clinical problem thought to be due to the reactivation of dormant tumor cells that disseminate before the primary tumor has been removed. How dormancy is established and ultimately reversed to drive recurrence is poorly understood. Here we introduce a novel mouse model of pancreatic cancer dormancy in which we establish distal pancreatic tumors by orthotopic injection, resect them four weeks later and then follow the mice for recurrence. We observed recurrence patterns and survival outcomes that mimic human patients undergoing surgery for pancreatic cancer where two thirds of the mice succumb to early metastatic recurrence (median survival 26 days) and one third of the mice (called dormant mice) live substantially long (median survival 554 days) without clinic evidence of disease yet harbor disseminated tumor cells in most organs of the body. Disseminated tumor cells isolated from the livers of dormant mice were quiescent, exhibited stem cell properties and upregulated the expression of Dec2, a circadian rhythm gene. Overexpression of Dec2 induced quiescence suggesting that it may be a driver of the dormant phenotype. Curiously, endogenous Dec2 actually increased the growth and metastasis of nondormant tumors. Dec2WT and Dec2 knockout cell lines were used to generate resectable orthotopic tumors in immune-competent mice, and loss of Dec2 decreased tumor growth, dissemination and metastasis, and the median survival of mice with DecWT tumors was 25 days whereas 70% of the mice with the otherwise isogenic Dec2KOs were still alive after 200 days. Notably, these differences in tumor size, dissemination, metastasis and survival were abrogated in nude mice, indicating an immune mediated mechanism. Dec2WT and Dec2KO cell lines expressed the same total amount of the antigen-presenting protein MHC-1, but much more of the MHC-1 was present on the surface of Dec2KO cell lines than on the Dec2WT cell lines. MHC-1 requires peptide loading before transport to the cell surface, and we see evidence for reduced production of small peptides in the DecKO cells. For instance the half-life of luciferase, a very potent immunogen in mice, was reduced in the Dec2KO cells, potentially providing small peptides for MHC-1 biosynthesis. Protein turnover may be upregulated to compensate for increases in translation, as ribosomal genes are more highly expressed in Dec2KO cells, including many c-Myc pathway genes. Indeed, Western blot analysis revealed upregulation of c-Myc protein in Dec2KO cells. These data suggest that Dec2 plays a novel role in the immune system by decreasing MHC-1 cell surface expression through decreasing peptide generation, protein translation and turnover. Citation Format: Chris R. Harris, Crissy Dudgeon, Orjola Prela, Lan Wang, Anthony Casabianca, Juliana Cazarin de Menezes, Christina Davidson, Paula Vertino, Brian Altman, Darren Carpizo. DEC2, a circadian rhythm transcription factor, promotes growth, metastasis and dormancy by facilitating immune cell invasion through decreasing cell surface expression of MHC-1 in a novel model of pancreatic cancer dormancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1287.

Hepatic mucinous cystic neoplasm (H-MCN) and intraductal papillary neoplasm (IPN-B) are rare mucinous biliary tumors with malignant potential. Both can present with proximal biliary obstruction and be difficult to distinguish from cholangiocarcinoma. We present one case of each (H-MCN, IPN-B), presenting with proximal biliary obstruction. We highlight the diagnostic challenges presented by these liver tumors and emphasize their indolent growth as one key distinguishing feature from cholangiocarcinoma. We also discuss their management including variations in surgical technique.

The axonal guidance receptor UNC5B is considered to be a tumor suppressor because it promotes apoptosis in the absence of its protein ligand, NTN1. But we find that UNC5B is not a tumor suppressor of pancreatic ductal adenocarcinomas (PDAC), and instead promotes metastasis. In TCGA data, UNC5B expression associates with poor patient outcome. In vivo, pancreatic cancer metastasis was completely eliminated by knocking out UNC5B from the genetically engineered KPC mouse model of PDACs, and was reduced upon knockout of UNC5B in a splenectomy model of liver metastasis. An inhibitor of NTN1, NP137, also reduced metastasis in vivo. In vitro, knockout of UNC5B from mesenchymal pancreatic cell lines was sufficient to reduce many metastatic traits including invasiveness, EMT, and aerobic glycolysis. YAP1 is a known target of UNC5B and was overexpressed in high UNC5B expressing cell lines, which were sensitive to the YAP1 inhibitor CA3. NP137 is currently in clinical trial for several tumor types and we have been investigating which patients might respond best to this drug. Using an antibody (D9M7Z) that recognizes an epitope in UNC5B that overlaps with the caspase-3 cleavage site that is critical for UNC5B's apoptotic functions, we found two isoforms in murine and human PDACs: one isoform that contains the caspase-3-containing epitope as well as a previously-unreported isoform that to lack it. Cells expressing the caspase-3 site were much more sensitive to NP137. We also discovered genetic alterations in patient samples that induce expression of UNC5B. For instance, UNC5B was recurrently amplified in PDACs and these amplifications were highly focal to the UNC5B locus; also, UNC5B expression was increased by mutations of ARID1A, a component of the SWI/SNF transcription complex that is recurrently mutated in pancreatic adenocarcinomas. ARID1A mutations caused cell lines to become mesenchymal, but the cells returned to an epithelial phenotype upon knockout of UNC5B. In current and future clinical trials, NP137 may particularly benefit patients with tumors that harbor mutations in ARID1A or ARID1B, focal amplifications of UNC5B, and/or high expression of the caspase-3-containing isoform of UNC5B. Citation Format: Chris R. Harris, Orjola Prela, Lan Wang, Anthony Casabianca, Wade Narrow, Zachary Sechrist, Tracy Withers, Cory Shields, Asra Asad, Aram Hezel, Darren Carpizo. UNC5B promotes EMT and metastasis of pancreatic adenocarcinomas and expresses different isoforms that impact sensitivity to Netrin-1 blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1286.

606 Background: Standard of care for early-stage resectable pancreatic cancer (PC) includes a combination of surgical resection and chemotherapy. Frequently, CA 19-9 is used as a biomarker to monitor treatment effect and has prognostic significance. We evaluated the impact of CA 19-9 on overall survival (OS) in patients with clinical stage I PC (cT1N0 and cT2N0) utilizing the National Cancer Database (NCDB). Methods: The NCDB was queried between 2010 and 2014 to identify patients with clinical stage I PC. Patients who had missing or undocumented CA 19-9 value at diagnosis were excluded. Demographic and clinical characteristics were analyzed. Patients were stratified into two cohorts based on the CA 19-9 value at diagnosis – CA 19-9 < 98 U/mL and CA 19-9 > 98 U/mL. Univariable and multivariable analyses were performed, and variables associated with OS were identified. Kaplan-Meier survival curves were computed to compare the OS between the two cohorts. Results: A total of 12,480 patients met our inclusion criteria. A majority of patients were female (51.9%), white (84.4%), with a median age of 70 years. Nearly, half the patients received care in an academic/research program (49.5%). A majority of patients had tumors located in the head of the pancreas (71.9%), and received single-agent (35.1%) or multiagent (22.9%) chemotherapy. Over half the patients (6505 patients, 52.1%) had a CA 19-9 value > 98 U/mL. A CA 19-9 value > 98 U/mL in patients predicted a significantly shorter median OS of 12.1 months compared to 19.4 months in patients with a CA 19-9 < 98 U/mL, p<0.0001 (Table). The 5-year OS rate was 9.9% in patients with a CA 19-9 value of > 98 U/mL compared to a 5-year OS rate of 18.1% for patients with a CA 19-9 value < 98 U/mL. On multivariable analysis, CA 19-9 > 98 compared to CA 19-9 < 98 (HR 1.53, p<0.001) and black race compared to white race (HR 1.10, p<0.001) was associated with worse survival, whereas tumor location in the body and tail compared to the head (HR 0.82, p<0.001), single-agent (HR 0.55, p<0.001) and multiagent (HR 0.55, p<0.001) chemotherapy compared to no chemotherapy, independently predicted improved OS. Conclusions: This is the first National Cancer Database study to demonstrate the prognostic value of CA 19-9 in patients with clinical stage I pancreatic cancer, with a value < 98 U/mL predicting improved survival. Clinical stage I pancreatic cancer patients appear to derive a significant benefit from chemotherapy, including single and multiagent chemotherapy, irrespective of the CA 19-9 value.[Table: see text]

Hepatic cavernous haemangioma is a benign tumour of vascular origin found within the liver. Often incidentally diagnosed, the management of these vascular masses is frequently determined by the size of the mass and symptoms associated with its compression of adjacent structures. Tumours >10 cm are known as giant haemangiomas and are associated with increased risks of compression symptoms, coagulopathies and haemorrhage. Known to express hormone receptors for oestrogen, intervention for these masses remains controversial in the setting of pregnancy where concerns for tumour growth and life-threatening complications are increased. Here we present the case of a woman in her 30s recently diagnosed with a giant haemangioma who is found to be pregnant, their management and a review of the literature.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a proclivity for early metastasis. Resection remains the only chance for long term survival though most patients die from metastatic recurrence. While most patients recur within the first two years, many develop recurrence much later indicating they harbor dormant disseminated tumor cells (dDTCs). Currently there are no murine models which recapitulate this disease pattern and as a result pancreatic cancer dormancy is poorly understood. We sought to better understand PDAC dormancy using a novel murine model of human pancreatic cancer from which we investigate the genetic and molecular contributions to dormancy. A model of resected PDAC was developed using murine PDAC cells expressing luciferase/mCherry orthotopically implanted into FVB hosts. Primary tumors are resected after 4 weeks and mice followed for recurrence. dDTCs’ are harvested from the livers of mice without evidence of recurrence by fluorescence activated cell sorting (FACS) and subjected to transcriptomic profiling using single cell RNA sequencing. Dec2’s contribution to dormancy was evaluated by overexpression and knockout using CRISPR. Overall survival in the mouse model mirrored 41,552 stage I, II PDAC patients from the National Cancer Database with similar frequency and location of recurrence. One third of mice exhibited latent recurrence with median survival of 568 days before succumbing to recurrence. These mice were used to study dDTCs. Transcriptomic profiling of FACS sorted dDTCs revealed a distinct transcriptome from primary tumors and early recurrences, indicating cell plasticity. dDTCs exhibited decreased proliferation markers and upregulated genes involved in immune modulation, cell stemness, linoleic acid (LA) metabolism, and Dec2. dDTCs were resistant to chemotherapy. An in vitro model of dormancy was constructed in which LA treatment inhibited cell proliferation and increased Dec2. Dec2 overexpression resulted in cell quiescence, and knockout increased apoptosis with LA exposure. Dec2-KO cells implanted in the murine model dramatically improved survival compared to Dec-WT cells (Dec2-WT median survival 30 days, Dec2-KO median survival was not reached, p=0.013). Livers of mice in the resection model where Dec2-KO cells were used had decreased dDTC burden with fewer mice showing detectable luciferase gDNA (p<0.01) indicating that loss of Dec2 reduced survival of dDTC’s. This is the first murine model of pancreatic cancer dormancy that recapitulates outcomes of resected PDAC patients. These studies reveal pancreatic cancer dormancy is characterized by a distinct, plastic cellular state characterized by chemotherapy resistance. Dec2 appears required for dormancy, its absence leads to disseminated tumor cell apoptosis. This suggests Dec2 may be a therapeutic target in pancreatic cancer dormancy. Citation Format: Anthony S. Casabianca, Chris Harris, Crissy Dudgeon, Darren R. Carpizo. Dec2, a circadian rhythm gene is necessary for disseminated tumor cell survival in a novel murine model of pancreatic cancer dormancy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 916.

Background Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of unknown etiology and unpredictable natural history. To date, no large-scale studies have been published evaluating this disease due to its rare occurrence. Methods The National Cancer Database was reviewed between 2004 and 2016 to identify patients with HEH. Univariate analysis with overall survival (OS) was performed by Cox proportional hazards model. Kaplan-Meier method was used to create OS curves and compared using the log-rank test. Results We identified 229 patients with HEH. The majority of patients were female (61.1%), white (84.3%), and had a Charlson-Deyo score of 0 (75%). Chemotherapeutic intervention was seen in 26% of the patients while 33% received surgical intervention in the form of wedge/segmental liver resection (n = 27), hepatectomy lobectomy/extended lobectomy (n = 18), and liver transplant (n = 22). Five-year survival in surgical patients was 90.5%, 66.5% and 81%, respectively (p = 0.485). Age greater than 55 years (hazard ratio [HR], 2.78; p < 0.001), Asian ethnicity compared to white (HR, 2.84; p = 0.012), and a higher Charlson-Deyo score (score 1: HR, 2.28; p < 0.001 and score >= 2: HR, 2.76; p = 0.011) were associated with worse OS. Conclusion Treatment for HEH remains variable with only a third of the patients undergoing surgery. International collaboration is necessary to determine the optimal treatment for this rare disease.

BackgroundGallbladder cancer (GBC) is the most common biliary malignancy frequently metastatic at diagnosis with poor prognosis. While surgery remains the standard for early-stage GBC, the role of surgery in patients with metastatic gastrointestinal cancers is expanding due to improvements in systemic therapies. We sought to evaluate the survival of patients with stage IV GBC undergoing surgery in an era of improved multi-agent systemic therapy.MethodsA retrospective review of the National Cancer Database was performed. Patients with stage IV GBC who underwent systemic therapy were included. Patients who received radiation therapy, palliative therapy or had missing survival data were excluded. Univariable and multivariable analysis was performed.Results4,145 patients were identified between 2004 and 2016. Mean age was 69. Surgery combined with systemic therapy predicted improved median survival compared with chemotherapy alone (11.1mo versus 6.8mo, HR 0.65, p < 0.001). Additionally, receipt of treatment after 2011 predicted improved survival (HR 0.86, p < 0.001). Patients treated with multi-agent chemotherapy in combination with surgery were associated with the greatest hazard ratio benefit (0.40, p < 0.001) versus single agent therapy alone.ConclusionPatients with stage IV gallbladder cancer treated with a combination of surgery and chemotherapy are associated with an improved overall survival compared to chemotherapy alone. Patients receiving care during the more recent era demonstrated improved survival. These results support a role for surgery in selected patients with stage IV gallbladder cancer receiving chemotherapy.

Carbohydrate antigen (CA) 19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB). The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I–II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98 U/mL and CA19-9 ≥ 98 U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported. Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1

Axon guidance pathways have often been linked to tumorigenesis by informatics analyses, but their roles in tumorigenesis are not well understood at a functional level. Here we show that axon guidance receptor UNC5B and its ligand, NTN1, promote the metastasis of pancreatic ductal adenocarcinomas (PDACs) by reducing anoikis and by promoting a mesenchymal phenotype. In vivo, removal of two floxed UNC5B alleles eliminated PDAC metastasis in the genetically engineered KPC mouse model, and also reduced metastasis by xenografted PDAC cell lines. PDAC metastasis also decreased upon treatment of animals with NP137, an antibody that targets NTN1. In vitro, deletion of UNC5B from pancreatic adenocarcinoma cell lines reduced invasiveness, and was sufficient to convert PDAC cell lines from an epithelial to a mesenchymal state. UNC5B also increased YAP1 expression but decreased anoikis; anoikis could then be restored by treatment with the YAP1 inhibitor CA3. Clinically, UNC5B expression associated with poor outcomes in patients with pancreatic adenocarcinomas. UNC5B and NTN1 expression increased upon truncation of the SWI/SNF component ARID1A, which is recurrently mutated in PDACs. Highly focal amplifications of UNC5B were also observed in some patient samples, and were mutually exclusive with mutations in ARID1A or ARID1B. NP137 is currently in clinical trials for various cancers, and may benefit pancreatic adenocarcinoma patients, particularly those with UNC5B amplifications or with ARID1A/ARID1B mutations. Citation Format: Chris Harris, Anthony Casabianca, Zach Sechrist, Cory Shields, Wade Narrow, Tracy Withers, Crissy Dudgeon, Mike O'Dell, Aram Hezel, Darren Carpizo. The axon guidance receptor UNC5B is a driver of pancreatic cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B021.

Introduction Following resection of pancreatic acinar cell carcinoma (PACC) distant recurrence remains high. We utilized the national cancer database (NCDB) to evaluate the role of systemic therapy in early-stage resected PACC. Methods We queried the NCDB registry from 2004 to 2015 for patients with pathologic stage I-IIB PACC. For each stage, patients who underwent surgery alone (SA) were compared to patients who received systemic and/or radiation therapy in addition to surgery (surgery + therapy [S + T]). Results A total of 271 patients (101 pI, 81 pIIA, and 89 pIIB) were analyzed. Of all clinically node positive patients (n = 41), the majority (n = 32, 78%) had node-positive disease at resection (pIIB). SA was performed in 112 patients (41.3%), whereas 159 (58.7%) patients received S + T. There was no difference in overall survival (OS) between S + T and SA with respect to pI or pIIA disease. In pIIB disease, S + T was associated with improved OS compared to SA (34.9 vs. 16.9 months, p = 0.031). Single-agent chemotherapy was associated with improved OS for pIIB disease when compared to SA (hazard ratio: 0.38, 95% confidence interval: 0.16, 0.83). Conclusion In resectable PACC, the survival benefit of adjuvant therapy is limited to pathologic stage IIB disease. This benefit is evident even in patients treated with single-agent chemotherapy.

3601 Background: A minimum of 12 lymph nodes are required during colectomy to accurately stage colon cancer. Prior studies in stage II colon cancer patients demonstrate association of inadequate lymph node examination (LNE) with worse overall survival (OS). No large-scale analogous studies related to LNE have been completed in stage I colon cancer patients. We evaluated patients with stage I colon cancer to determine the association between lymph node yield and OS. Methods: We reviewed the National Cancer Database between 2004-2015 to identify patients with pathologic stage I colon cancer (pT1N0 or pT2N0) who underwent definitive surgical resection. Patients who received radiation therapy or had missing values were excluded. Clinical and demographic characteristics were analyzed. Based on LNE, patients were stratified into 4 cohorts (LNE, 0-5, 6-11, 12-19, 20+) and 2 cohorts (0-11, 12+). Univariable and multivariable analyses were performed to identify variables associated with OS. Kaplan-Meier survival curves were computed to compare the cohorts. Results: We included 81,909 patients for analyses. Median age at diagnosis was 69. A majority were female (51.1%), white (83.8%), received care in a community cancer program (59.5%), and had a Charlson-Deyo score of 0 (66.6%). Only 0.7% of patients had a margin positive resection with a 2.5cm median tumor size. Patients were similarly split between pT1 and pT2. Suboptimal LNE was noted in 27.8% of patients. Patients with LNE were distributed - 10.7% (0-5), 17.1% (6-11), 43.4% (12-19) and 28.9% (20+). Postoperative 30-day mortality was 1.9%. 521 (0.7%) received systemic therapy. Ten-year survival in patients with 0-5 LNE was 52.8% compared to 60.1% with 20+ LNE. On multivariable analyses, patients aged ≥ 69, male sex, increasing tumor size (quartile), pT2 staging and a higher Charlson-Deyo score independently predicted worse OS (p < 0.001). LNE categories were significantly associated with OS (p < 0.001) (Table). On regrouping into 0-11 and 12+ LNE groups, 0-11 LNE group predicted worse OS (HR 1.22, p < 0.001). On multivariable analysis, the above variables continued to show similar association with OS (p < 0.001). Conclusions: Our study demonstrates that lymph node yield is associated with overall survival in patients with stage 1 colon cancer undergoing surgical resection. Furthermore, patients with suboptimal lymph node yield are associated with an inferior overall survival compared to those with optimal lymph node yield. Moreover, this study finds that a large number of patients ( > 25%) continue to have suboptimal lymph node yields. Future efforts should focus on improving the lymph node yield with optimal efforts by the surgeon and pathologist. Future studies should examine the role of systemic therapy in patients with inadequate lymph node yield.[Table: see text]

Pancreatic cancer (PC) is a highly lethal malignancy characterized by local tumor aggressiveness and early metastatic dissemination. While surgical resection is used to treat localized cancers, the majority of patients do recur suggesting the presence of disseminated tumor cells (DTC) at the time of surgery. These DTC9s represent minimal residual disease. While most patients recur early, a subset recur late due to the reactivation of dormant tumor cells. Currently, the mechanisms of cancer dormancy are poorly understood in part due to a lack of animal models that reflect human disease. Here we describe a murine model of PC dormancy that mimics outcomes in resected human patients. Using single-cell transcriptomics and an assay for chromatin accessibility, we found dormancy is a distinct cellular state from pre or post-dormant cancer cells. Mechanisms of dormancy include increased expression of transcriptional repressor Dec2, which functionally drives quiescence, and monoallelic suppression of mutant KRAS by DNA methylation. Pathway analysis of dormant tumor cell transcriptomics indicated an up-regulation of enzymes involved in linoleic acid metabolism among others. Linoleic acid treatment of tumor cells resulted in inhibited cell proliferation, decreased tumor growth, and an increase in Dec2 expression. We have identified a dormancy gene signature that is distinct from non-dormant PC cells and found that this correlates with human resected patients with long term survivals, and inversely in patients with short term survivals. We demonstrate that dormancy is characterized by large scale transcriptomic changes and global chromatin remodeling. We developed methods for isolating DTCs from the livers of early stage PC patients undergoing resection. Using these methods we have found that the murine dormancy signature correlated with the gene expression of the DTCs and not primary tumor cells indicating this dormancy signature has human relevance with potential novel therapeutic avenues. Citation Format: Anthony S. Casabianca, Crissy Dudgeon, Chris Harris, Subhajyoto De, Mihir Shah, Arthur Roberts, Eric Collisson, Vinod Balachandran, Darren Carpizo. A genetic signature of cancer dormancy: implications for human disease derived from a novel murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 121.