Metabolic Pathway Tracer for Breast Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Rutgers, The State University of New Jersey
No Placebo Group
Trial Summary
What is the purpose of this trial?To analyze the metabolic activity of Hormone Receptor Positive (HR+)/Her 2 Negative (Her2-) Breast cancer.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment U-13C-glucose for breast cancer?
Research shows that using 13C6-glucose can help track how cancer cells process glucose, which is important for understanding tumor metabolism. This method has been used to study glucose metabolism in different types of cancer, suggesting it could be useful in assessing breast cancer as well.
12345Is U-13C-glucose safe for use in humans?
Research involving U-13C-glucose in mice has shown it can be used safely to trace metabolic processes without causing stress or harm. However, specific safety data for humans is not provided in the available studies.
12467How is the treatment U-13C-glucose unique for breast cancer?
U-13C-glucose is unique because it acts as a tracer to study the metabolic pathways in breast cancer cells, helping researchers understand how these cells process glucose differently from normal cells. This approach is different from standard treatments as it focuses on mapping cancer metabolism rather than directly targeting cancer cells for destruction.
128910Eligibility Criteria
This trial is for individuals with HR+/HER2- breast cancer, who haven't had neoadjuvant therapy and are set for curative surgery. They must be willing to provide tissue samples during surgery and not be part of another clinical study or have other active cancers.Inclusion Criteria
I am a candidate for surgery to remove my cancer and have not had any pre-surgery treatments.
My breast cancer is hormone receptor positive and HER2 negative.
I agree to have small samples of my tumor and normal tissue taken during surgery for research.
My breast cancer is in an early stage (I, II, or III).
Exclusion Criteria
I have another active cancer besides the one being treated.
My breast cancer is either triple negative or HER2 positive.
Participant Groups
The trial studies how hormone receptor-positive, HER2-negative breast cancer cells process sugar by using a special form of glucose called U-13C-glucose during surgical resection of the tumor.
1Treatment groups
Experimental Treatment
Group I: Metabolic activity of Hormone Receptor Positive (HR+)/Her 2 Negative (Her2-) Breast cancerExperimental Treatment1 Intervention
Administration of U-13C-glucose to participants with early-stage HR+/Her2- breast cancer fitting criteria, will be done intraoperatively at the time of resection, as well as blood sample collection.
This will allow for in depth evaluation of glycolysis as well as TCA cycle, lipid and amino acid metabolism and comprehensive genomic analyses to complement the metabolic assays that will be done by the Ludwig Institute of Cancer Research. HR+/Her2- breast cancer subtype is chosen for this feasibility pilot study given that metabolic studies have not been done in this subtype of breast cancer and it makes up the majority of breast cancer cases.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
RWJBarnabas HealthNew Brunswick, NJ
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Who is running the clinical trial?
Rutgers, The State University of New JerseyLead Sponsor
Ludwig Institute for Cancer ResearchCollaborator
References
Monitoring the transport and phosphorylation of 2-deoxy-D-glucose in tumor cells in vivo and in vitro by 13C nuclear magnetic resonance spectroscopy. [2019]We describe the use of 2-deoxy-D-[6-13C]glucose to follow simultaneously, by 13C NMR, both transport and phosphorylation to its 6-phosphate form, in MCF-7 breast cancer cells in vitro and in vivo in subcutaneous tumors in nude mice.
Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing. [2019]Delivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive introduction of 13C6-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive 13C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of 13C6-glucose feeding. Applying this approach to patient-derived lung tumor xenografts (PDTX), we show that the liver supplies glucose-derived Gln via the blood to the PDTX to fuel Glu and glutathione synthesis while gluconeogenesis occurs in the PDTX. Comparison of PDTX with ex vivo tumor cultures and arsenic-transformed lung cells versus xenografts reveals differential glucose metabolism that could reflect distinct tumor microenvironment. We further found differences in glucose metabolism between the primary PDTX and distant lymph node metastases.
Reverse Warburg Effect-Related Mitochondrial Activity and 18F-FDG Uptake in Invasive Ductal Carcinoma. [2022]Label="PURPOSE" NlmCategory="OBJECTIVE">We evaluated the relationship between fluorine-18 fluoro-2-deoxy-glucose (18F-FDG) uptake and mitochondrial activity in cancer cells and investigated the prognostic implications of this relationship in patients with invasive ductal carcinoma of the breast (IDCB).
Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate. [2021]Evaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR, were incubated for 3 h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated for 18 h in the presence of [U-13C6]glucose. 13C-enrichment and isotopologue profiles of key amino acids were monitored by gas chromatography-mass spectrometry (GC/MS), in order to monitor the impacts of the radionuclide-treatment upon glucose metabolism. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of 13C from [U-13C6]glucose into alanine, aspartate, glutamate, glycine, proline and serine. In sharp contrast, the same amino acids did not display less 13C-enrichments during treatment of the LN18 cells. The data indicate early treatment response of the bladder cancer cells, but not of the glioma cells though cell lines were killed following 213Bi-anti-EGFR-MAb treatment. The pilot study shows that the 13C-labelling approach is a valid tool to assess the responsiveness of cancer cells upon radionuclide-treatment in considerable metabolic detail.
Predicting the prognoses of breast carcinoma patients with positron emission tomography using 2-deoxy-2-fluoro[18F]-D-glucose. [2022]Positron emission tomography (PET) with 2-deoxy-2-fluoro[18F]-D-glucose (FDG) can provide quantitative information about tumor glucose metabolism. The prognostic value of this technique was evaluated for breast carcinoma patients.
Synthesis and characterization of 6-deoxy-6-fluoro-D-fructose as a potential compound for imaging breast cancer with PET. [2009]FDG-based imaging with positron emission tomography (PET) has been widely used in the detection of cancer, but has not reached its full potential. In breast cancer, the glucose/fructose transporter GLUT2 and the fructose transporter GLUT5 are known to be overexpressed in transformed tissues, implicating that a fructose-based analogue would be a useful target for the improved imaging of breast cancer. We have successfully synthesized the fluorinated fructose compound, 6-deoxy-6-fluoro-D-fructose (6FDF) and examined its potential for transport and accumulation in breast cancer cells. Expression analysis of GLUT isoforms was performed on two GLUT5 expressing breast cancer cell lines using western blotting and immunocytochemistry. Uptake and inhibition studies were undertaken using [14C]-labelled hexoses. Transport inhibition studies showed dose dependent inhibition of fructose transport in both cell lines by the newly synthesized 6-deoxy-6-fluoro-D-fructose (6FDF). Also, near linear uptake over time of [14C]-labelled 6FDF was observed in both cell lines. It appears that 6FDF may have great promise for use in in vivo PET imaging of breast cancer. Ongoing work will confirm the efficacy of this compound in imaging in mouse models.
Radiopharmacological evaluation of 6-deoxy-6-[18F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer. [2016]Several clinical studies have shown low or no expression of GLUT1 in breast cancer patients, which may account for the low clinical specificity and sensitivity of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) used in positron emission tomography (PET). Therefore, it has been proposed that other tumor characteristics such as the high expression of GLUT2 and GLUT5 in many breast tumors could be used to develop alternative strategies to detect breast cancer. Here we have studied the in vitro and in vivo radiopharmacological profile of 6-deoxy-6-[(18)F]fluoro-D-fructose (6-[(18)F]FDF) as a potential PET radiotracer to image GLUT5 expression in breast cancers.
Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells. [2021](13)C metabolic flux analysis (MFA) is the most comprehensive means of characterizing cellular metabolic states. Uniquely labeled isotopic tracers enable more focused analyses to probe specific reactions within the network. As a result, the choice of tracer largely determines the precision with which one can estimate metabolic fluxes, especially in complex mammalian systems that require multiple substrates. Here we have experimentally determined metabolic fluxes in a tumor cell line, successfully recapitulating the hallmarks of cancer cell metabolism. Using these data, we computationally evaluated specifically labeled (13)C glucose and glutamine tracers for their ability to precisely and accurately estimate fluxes in central carbon metabolism. These methods enabled us to identify the optimal tracer for analyzing individual fluxes, specific pathways, and central carbon metabolism as a whole. [1,2-(13)C(2)]glucose provided the most precise estimates for glycolysis, the pentose phosphate pathway, and the overall network. Tracers such as [2-(13)C]glucose and [3-(13)C]glucose also outperformed the more commonly used [1-(13)C]glucose. [U-(13)C(5)]glutamine emerged as the preferred isotopic tracer for the analysis of the tricarboxylic acid (TCA) cycle. These results provide valuable, quantitative information on the performance of (13)C-labeled substrates and can aid in the design of more informative MFA experiments in mammalian cell culture.
Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics. [2020]Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using 13C6-glucose, 13C-1+2-glucose, 13C5,15N2-Gln, 13C3-glycerol, and 13C8-octanoate as tracers. These tracers were designed to probe the central energy producing and anabolic pathways (glycolysis, pentose phosphate pathway, Krebs Cycle, glutaminolysis, nucleotide synthesis and lipid turnover). We found that glycolysis was not associated with the rate of breast cancer cell proliferation, glutaminolysis did not support lipid synthesis in primary breast or breast cancer cells, but was a major contributor to pyrimidine ring synthesis in all cell types; anaplerotic pyruvate carboxylation was activated in breast cancer versus primary cells. We also found that glucose metabolism in individual breast cancer cell lines differed between in vitro cultures and tumor xenografts, but not the metabolic distinctions between cell lines, which may reflect the influence of tumor architecture/microenvironment.
Optimized protocol for stable isotope tracing and steady-state metabolomics in mouse HER2+ breast cancer brain metastasis. [2022]Analyzing the metabolic dependencies of tumor cells is vital for cancer diagnosis and treatment. Here, we describe a protocol for 13C-stable glucose and glutamine isotope tracing in mice HER2+ breast cancer brain metastatic lesions. We describe how to inject cancer cells intracardially to generate brain metastatic lesions in mice. We then detail how to perform 13C-stable isotope infusion in mice with established brain metastasis. Finally, we outline steps for sample collection, processing for metabolite extraction, and analyzing mass spectrometry data. For complete details on the use and execution of this protocol, please refer to Parida et al. (2022).