Metabolic Pathway Analysis for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Rutgers, The State University of New Jersey
Must not be taking: Chemotherapy, Immunotherapy, Biologic therapy
Disqualifiers: Active malignancy, Pregnancy, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This clinical trial investigates the nutrients pancreatic cancers depend on in which to survive and the processes these tumors use (metabolism) to obtain these nutrients. Giving U-13C-glucose during surgery may allow doctors to trace the metabolic activity of pancreatic cancer in research experiments done in the laboratory. These experiments may help researchers understand how cancer cells manage their nutrients when compared to normal pancreatic cells.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are receiving any anti-cancer therapy, you may not be eligible for this trial unless you are part of the group treated with neoadjuvant chemotherapy.
What data supports the effectiveness of this treatment for pancreatic cancer?
Research indicates that pancreatic cancer cells have altered metabolic pathways, which can be targeted for treatment. The use of uniformly-labeled [13C]glucose helps in understanding these metabolic changes, potentially leading to more effective therapies by targeting the cancer's unique metabolism.12345
Is the treatment for metabolic pathway analysis in pancreatic cancer safe for humans?
How is Therapeutic Conventional Surgery different from other treatments for pancreatic cancer?
Therapeutic Conventional Surgery, also known as Transoral Surgical Resection, is unique because it involves a surgical approach to remove cancerous tissue, which is different from other treatments that focus on targeting the metabolic pathways of pancreatic cancer cells. This surgery may offer a direct method to physically remove tumors, whereas other treatments often aim to disrupt the cancer's altered metabolism.13458
Research Team
Howard S. Hochster
Principal Investigator
Rutgers Cancer Institute of New Jersey
Eligibility Criteria
This trial is for adults with pancreatic adenocarcinoma, eligible for surgery. It includes both untreated patients and those who've had chemotherapy but no other cancer treatments like radiation or immunotherapy. Participants must understand the study's experimental nature and consent to biopsies during surgery.Inclusion Criteria
I agree to have extra biopsies taken during my surgery for research.
All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry
I am 18 years old or older.
See 2 more
Exclusion Criteria
I am currently undergoing or will undergo chemotherapy, immunotherapy, or biologic therapy.
Is of child-bearing potential who has not had a recent negative pregnancy test done outside of this clinical trial (i.e., as part of standard preparation for diagnosis and treatment for her cancer)
I have another active cancer besides the one being treated.
See 1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive uniformly-labeled [13C]glucose intravenously over 10 minutes and then over up to 120 minutes until time of biopsy, followed by surgery and biopsy per standard of care
1 day
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 2 years
Treatment Details
Interventions
- Biopsy (Procedure)
- Therapeutic Conventional Surgery (Procedure)
- Uniformly-labeled [13C]glucose (Metabolic Pathway Inhibitor)
Trial OverviewThe trial studies how pancreatic cancer cells manage nutrients by using a special form of glucose given during surgery. Researchers will compare the metabolism of cancerous and normal cells from biopsies to better understand the disease.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Basic science (uniformly-labeled [13C]glucose)Experimental Treatment3 Interventions
Patients receive uniformly-labeled \[13C\]glucose IV over 10 minutes and then over up to 120 minutes until time of biopsy. Patients then undergo surgery and biopsy per standard of care.
Therapeutic Conventional Surgery is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Therapeutic Conventional Surgery for:
- Resectable p16+ Locally Advanced Oropharynx Cancer
🇪🇺 Approved in European Union as Transoral Surgical Resection for:
- HPV-positive oropharyngeal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Rutgers, Cancer Institute of New JerseyNew Brunswick, NJ
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
Cooperman Barnabas Medical Center (Saint Barnabas Medical Center)Livingston, NJ
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Who Is Running the Clinical Trial?
Rutgers, The State University of New Jersey
Lead Sponsor
Trials
471
Patients Recruited
81,700+
National Cancer Institute (NCI)
Collaborator
Trials
14080
Patients Recruited
41,180,000+
References
Glucose metabolic phenotype of pancreatic cancer. [2018]To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.
Identification of the γ-glutamyl cycle as a novel therapeutic target and 5-oxoproline as a new biomarker for diagnosing pancreatic cancer. [2023]Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant solid tumours, and abnormal metabolic reprogramming in the tumour microenvironment is regarded as an important contributor to its pathogenesis.
Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets. [2023]Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers globally with a mortality rate exceeding 95% and very limited therapeutic options. A hallmark of PDAC is its acidic tumor microenvironment, further characterized by excessive fibrosis and depletion of oxygen and nutrients due to poor vascularity. The combination of PDAC driver mutations and adaptation to this hostile environment drives extensive metabolic reprogramming of the cancer cells toward non-canonical metabolic pathways and increases reliance on scavenging mechanisms such as autophagy and macropinocytosis. In addition, the cancer cells benefit from metabolic crosstalk with nonmalignant cells within the tumor microenvironment, including pancreatic stellate cells, fibroblasts, and endothelial and immune cells. Increasing evidence shows that this metabolic rewiring is closely related to chemo- and radioresistance and immunosuppression, causing extensive treatment failure. Indeed, stratification of human PDAC tumors into subtypes based on their metabolic profiles was shown to predict disease outcome. Accordingly, an increasing number of clinical trials target pro-tumorigenic metabolic pathways, either as stand-alone treatment or in conjunction with chemotherapy. In this review, we highlight key findings and potential future directions of pancreatic cancer metabolism research, specifically focusing on novel therapeutic opportunities.
Employing Metabolism to Improve the Diagnosis and Treatment of Pancreatic Cancer. [2018]Pancreatic ductal adenocarcinoma is on pace to become the second leading cause of cancer-related death. The high mortality rate results from a lack of methods for early detection and the inability to successfully treat patients once diagnosed. Pancreatic cancer cells have extensively reprogrammed metabolism, which is driven by oncogene-mediated cell-autonomous pathways, the unique physiology of the tumor microenvironment, and interactions with non-cancer cells. In this review, we discuss how recent efforts delineating rewired metabolic networks in pancreatic cancer have revealed new in-roads to develop detection and treatment strategies for this dreadful disease.
Metabolism addiction in pancreatic cancer. [2022]Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating central metabolic networks that fuel pancreatic tumors. Such pathways, including those of Ras signaling, glutamine-regulatory enzymes, lipid metabolism and autophagy, are directly affected by genetic mutations and extreme tumor microenvironments that typify pancreatic tumor cells. Elucidation of these metabolic networks can be expected to yield more potent therapies against this deadly disease.
Targeting neoadjuvant chemotherapy-induced metabolic reprogramming in pancreatic cancer promotes anti-tumor immunity and chemo-response. [2023]The molecular dynamics of pancreatic ductal adenocarcinoma (PDAC) under chemotherapy remain incompletely understood. The widespread use of neoadjuvant chemotherapy (NAC) provides a unique opportunity to investigate PDAC samples post-chemotherapy. Leveraging a cohort from Fudan University Shanghai Cancer Center, encompassing PDAC samples with and without exposure to neoadjuvant albumin-bound paclitaxel and gemcitabine (AG), we have compiled data from single-cell and spatial transcriptomes, proteomes, bulk transcriptomes, and metabolomes, deepening our comprehension of the molecular changes in PDACs in response to chemotherapy. Metabolic flux analysis reveals that NAC induces a reprogramming of PDAC metabolic patterns and enhances immunogenicity. Notably, NAC leads to the downregulation of glycolysis and the upregulation of CD36. Tissue microarray analysis demonstrates that high CD36 expression is linked to poorer survival in patients receiving postoperative AG. Targeting CD36 synergistically improves the PDAC response to AG both in vitro and in vivo, including patient-derived preclinical models.
Robust Validation and Comprehensive Analysis of a Novel Signature Derived from Crucial Metabolic Pathways of Pancreatic Ductal Adenocarcinoma. [2022]Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with a dismal prognosis. PDAC have extensively reprogrammed metabolic characteristics influenced by interactions with normal cells, the effects of the tumor microenvironment and oncogene-mediated cell-autonomous pathways. In this study, we found that among all cancer hallmarks, metabolism played an important role in PDAC. Subsequently, a 16-gene prognostic signature was established with genes derived from crucial metabolic pathways, including glycolysis, bile acid metabolism, cholesterol homeostasis and xenobiotic metabolism (gbcx). The signature was used to distinguish overall survival in multiple cohorts from public datasets as well as a validation cohort followed up by us at Shanghai Cancer Center. Notably, the gbcx-related risk score (gbcxMRS) also accurately predicted poor PDAC subtypes, such as pure-basal-like and squamous types. At the same time, it also predicted PDAC recurrence. The gbcxMRS was also associated with immune cells, especially CD8 T cells, Treg cells. Furthermore, a high gbcxMRS may indicate high drug sensitivity to irinotecan and docetaxel and CTLA4 inhibitor immunotherapy. Taken together, these results indicate a robust and reproducible metabolic-related signature based on analysis of the overall pathogenesis of pancreatic cancer, which may have excellent prognostic and therapeutic implications for PDAC.
Metabolic Alterations in Pancreatic Cancer Progression. [2020]Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic cells only, we compared the metabolic profile of KPC and orthotopic tumors with those obtained from KPC-tumor derived cell lines. We observed significant upregulation of glycolysis and the pentose phosphate pathway metabolites even at the early stages of pathogenesis. Other biosynthetic pathways also demonstrated a few common perturbations. While some of the metabolic changes in tumor cells are not detectable in orthotopic and spontaneous tumors, a significant number of tumor cell-intrinsic metabolic alterations are readily detectable in the animal models. Overall, we identified that metabolic alterations in precancerous lesions are maintained during cancer development and are largely mirrored by cancer cells in culture conditions.