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  • American Association for Cancer Research (AACR)  (18)
  • 1
    Online Resource
    Online Resource
    Abstract C65: Defining the implications of sugar derived metabolites (AGEs) to tamoxifen resistance and breast cancer disparity: Is it a question of lifestyle?
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 25, No. 3_Supplement ( 2016-03-01), p. C65-C65
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 25, No. 3_Supplement ( 2016-03-01), p. C65-C65
    Abstract: Tamoxifen is the most widely prescribed adjuvant therapy for estrogen receptor positive (ER+) breast cancer which comprises around 70% of all breast cancer cases. While many patients respond positively to tamoxifen treatment around 50% have de-novo resistance and approximately 30% of responsive tumors recur due to acquired drug resistance. Compared to European American women, African-American women with ER+ breast cancer, have worse progression-free and overall survival which coincides with increased resistance to anti-cancer therapies such as tamoxifen. Poor diet, low income, obesity and a lack of exercise are established lifestyle factors that are known to increase cancer burden and are often more prevalent in African American communities. Our research has identified a potential mechanistic link between sugar derived metabolites and estrogen receptor (ER) phosphorylation which provides a biological consequence of these established lifestyle factors which may directly impact tamoxifen therapy and minority health. Glycation is the non-enzymatic glycosylation of sugar moieties to biological macromolecules such as protein and DNA which produces reactive metabolites known as advanced glycation end products (AGE's). AGE's accumulate in our tissues as we grow older and drive many of the complications associated with diseases displaying health disparity including diabetes, metabolic syndrome, Alzheimer's and heart disease. Significantly, low income, obesity and an inactive lifestyle are established factors driving health disparity that also contribute to increased AGE accumulation levels in our bodies. In particular, AGE content in the Western Diet has consistently increased over the last 50 years due to increased consumption of sugar laden and cheap processed/manufactured foods which are high in reactive AGE metabolites and promote obesity. Due to the established links with lifestyle and cancer disparity we examined the biological effects of AGEs on tamoxifen therapy and found that elevated AGE levels can directly affect the response to tamoxifen treatment and promote tamoxifen resistance. AGE treatment in ER+ breast cancer cell models promoted tamoxifen resistance via the activation of the MAPK and AKT pathways leading to resistance associated changes in ERα phosphorylation. We also observed greater levels of AGE and its cognate receptor for AGE (RAGE) within breast cancer tumor and serum samples and showed a correlation between tumor progression and intra-tumoral AGE concentration. Strategies to eliminate or delay the occurrence of tamoxifen resistance would contribute to increasing overall survival in minority populations. By associating lifestyle-derived AGEs with tamoxifen resistance, opportunities exist for impacting cancer treatment initiatives arising through health and nutritional education and community outreach programs driven by basic, translational, epidemiological and cancer prevention research initiatives. Citation Format: Katherine R. Walter, Danzell M. Smith, Van Phan, Laura spruill, Marvella E. Ford, Victoria J. Findlay, David P. Turner. Defining the implications of sugar derived metabolites (AGEs) to tamoxifen resistance and breast cancer disparity: Is it a question of lifestyle? [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C65.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1538-7755.DISP15-C65
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 2
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    Abstract CT220: Expansion into multiple institutions for training in the use of the LUM Imaging System for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. CT220-CT220
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. CT220-CT220
    Abstract: Background: Obtaining tumor-free margins is critical for local control in breast conserving surgery. Currently, 20-40% of lumpectomy patients have positive margins that require surgical re-excision; this is a significant burden for patients, surgeons and the healthcare system. Therefore, it is of paramount importance that all cancer be resected from the tumor bed during lumpectomy surgery. The LUM Imaging System consists of a fluorescence-based imaging agent, a hand-held wide-field detector (LUM Imaging Device) used to image the surgical cavity walls intraoperatively in real-time after the resection of the main lumpectomy specimen, and a proprietary tumor detection algorithm that highlights regions in the tumor bed suspected to contain residual cancer. Methods: This multi-site clinical study is designed to refine the tumor detection algorithm developed in previous studies by correlating images generated by the LUM Imaging System with histopathology results. This is a prospective, interventional feasibility study and is an introductory arm to a pivotal study which will evaluate the safety and efficacy of the LUM Imaging System in reducing the positive margin rate during standard of care lumpectomies. Up to 250 adult female breast cancer patients undergoing lumpectomies are being enrolled at sixteen medical centers across the US. The novel imaging agent, LUM015, is injected into all enrolled subjects prior to their lumpectomy procedure. Subjects undergo the standard of care lumpectomy followed by intraoperative use of the LUM Imaging System which helps guide surgeons in identifying potential residual tumor tissue. The primary objective is to assess performance characteristics of the LUM Imaging System and to fine-tune the tumor detection algorithm. A secondary objective is to develop and refine the process of implementing the LUM Imaging System into institution-specific workflows during lumpectomies. A comprehensive process to evaluate the LUM Imaging System has been implemented and will be reported. This study is being conducted under an Investigational Device Exemption (IDE) approved by the FDA. To date, 72 subjects have been imaged using the LUM Imaging System. Successful implementation of standardized tissue collection, naming conventions, and LUM Imaging System training is intended to improve the quality and integrity of the data collected in the upcoming pivotal clinical trial to evaluate the safety and efficacy of the LUM Imaging System. This study is partially funded by a grant from the National Cancer Institute (award 1R44CA211013) to support biomedical technology development and Lumicell Inc. and is registered on Clinical Trials.gov as NCT03321929. Citation Format: Kate Smith, Jorge M. Ferrer, Barbara L. Smith, E. Shelley Hwang, Kelly K. Hunt, Daleela G. Dodge, Stephen E. Karp, Stephanie A. Valente, Irene L. Wapnir, Lynne P. Clark, David R. Carr, Peter D. Beitsch, Donna L. Dyess, Beth-Ann Lesnikoski, Peter W. Blumencranz, Nayana S. Dekhne, Linsey P. Gold, Anees Chagpar, Katherine Kacena, Livia Gjylameti, Felix Geissler. Expansion into multiple institutions for training in the use of the LUM Imaging System for intraoperative detection of residual cancer in the tumor bed of female subjects with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT220.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2019-CT220
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 3
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    Advances in Treating Metastatic Bone Cancer: Summary Statement for the First Cambridge Conference
    American Association for Cancer Research (AACR) ; 2006
    In:  Clinical Cancer Research Vol. 12, No. 20 ( 2006-10-15), p. 6209s-6212s
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 12, No. 20 ( 2006-10-15), p. 6209s-6212s
    Abstract: The First Cambridge Conference on Advances in Treating Metastatic Bone Cancer, a symposium held in Cambridge, Massachusetts, October 28 to 29, 2005, was convened to discuss recent advances and research related to the natural history of bone metastases and skeletal complications, bone cancer biology, treatment of myeloma and other solid tumors, and treatment-induced bone loss. The conference format combined brief presentations with extended periods of discussion. The conclusions reached during the 2-day meeting are summarized in this article and presented in more detail in the individual articles and accompanying discussion sessions that comprise the conference proceedings.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-06-1213
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
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  • 4
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    Toward a Drug Development Path That Targets Metastatic Progression in Osteosarcoma
    American Association for Cancer Research (AACR) ; 2014
    In:  Clinical Cancer Research Vol. 20, No. 16 ( 2014-08-15), p. 4200-4209
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 20, No. 16 ( 2014-08-15), p. 4200-4209
    Abstract: Despite successful primary tumor treatment, the development of pulmonary metastasis continues to be the most common cause of mortality in patients with osteosarcoma. A conventional drug development path requiring drugs to induce regression of established lesions has not led to improvements for patients with osteosarcoma in more than 30 years. On the basis of our growing understanding of metastasis biology, it is now reasonable and essential that we focus on developing therapeutics that target metastatic progression. To advance this agenda, a meeting of key opinion leaders and experts in the metastasis and osteosarcoma communities was convened in Bethesda, Maryland. The goal of this meeting was to provide a “Perspective” that would establish a preclinical translational path that could support the early evaluation of potential therapeutic agents that uniquely target the metastatic phenotype. Although focused on osteosarcoma, the need for this perspective is shared among many cancer types. The consensus achieved from the meeting included the following: the biology of metastatic progression is associated with metastasis-specific targets/processes that may not influence grossly detectable lesions; targeting of metastasis-specific processes is feasible; rigorous preclinical data are needed to support translation of metastasis-specific agents into human trials where regression of measurable disease is not an expected outcome; preclinical data should include an understanding of mechanism of action, validation of pharmacodynamic markers of effective exposure and response, the use of several murine models of effectiveness, and where feasible the inclusion of the dog with naturally occurring osteosarcoma to define the activity of new drugs in the micrometastatic disease setting. Clin Cancer Res; 20(16); 4200–9. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-13-2574
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 5
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    Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 12 ( 2015-06-15), p. 2489-2500
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 12 ( 2015-06-15), p. 2489-2500
    Abstract: Resistance to targeted EGFR inhibitors is likely to develop in EGFR-mutant lung cancers. Early identification of innate or acquired resistance mechanisms to these agents is essential to direct development of future therapies. We describe the detection of heterogeneous mechanisms of resistance within populations of EGFR-mutant cells (PC9 and/or NCI-H1975) with acquired resistance to current and newly developed EGFR tyrosine kinase inhibitors, including AZD9291. We report the detection of NRAS mutations, including a novel E63K mutation, and a gain of copy number of WT NRAS or WT KRAS in cell populations resistant to gefitinib, afatinib, WZ4002, or AZD9291. Compared with parental cells, a number of resistant cell populations were more sensitive to inhibition by the MEK inhibitor selumetinib (AZD6244; ARRY-142886) when treated in combination with the originating EGFR inhibitor. In vitro, a combination of AZD9291 with selumetinib prevented emergence of resistance in PC9 cells and delayed resistance in NCI-H1975 cells. In vivo, concomitant dosing of AZD9291 with selumetinib caused regression of AZD9291-resistant tumors in an EGFRm/T790M transgenic model. Our data support the use of a combination of AZD9291 with a MEK inhibitor to delay or prevent resistance to AZD9291 in EGFRm and/or EGFRm/T790M tumors. Furthermore, these findings suggest that NRAS modifications in tumor samples from patients who have progressed on current or EGFR inhibitors in development may support subsequent treatment with a combination of EGFR and MEK inhibition. Cancer Res; 75(12); 2489–500. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-14-3167
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 6
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    Advancing Treatment for Metastatic Bone Cancer: Consensus Recommendations from the Second Cambridge Conference
    American Association for Cancer Research (AACR) ; 2008
    In:  Clinical Cancer Research Vol. 14, No. 20 ( 2008-10-15), p. 6387-6395
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 14, No. 20 ( 2008-10-15), p. 6387-6395
    Abstract: Purpose: Summarize current knowledge, critical gaps in knowledge, and recommendations to advance the field of metastatic bone cancer. Experimental Design: A multidisciplinary consensus conference was convened to review recent progress in basic and clinical research, assess critical gaps in current knowledge, and prioritize recommendations to advance research in the next 5 years. The program addressed three principal topics: biology of metastasis, preserving normal bone health, and optimizing bone-targeted therapies. Results: A variety of specific recommendations were identified as important to advance research and clinical care over the next 5 years. Conclusions: Priorities for research in bone biology include characterizing components of the stem cell niche in bone, developing oncogenic immunocompetent animal models of bone metastasis, and investigating the unique contribution of the bone microenvironment to tumor growth and dormancy. Priorities for research in preserving normal bone health include developing methods to measure and characterize disseminating tumor cells, assessing outcomes from the major prevention trials currently in progress, and improving methodologies to assess risks and benefits of treatment. Priorities for optimizing bone-targeted therapies include advancing studies of serum proteomics and genomics to reliably identify patients who will develop bone metastases, enhancing imaging for early detection of bone metastases and early response evaluation, and developing new tests to evaluate response to bone-directed treatments.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-08-1572
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 7
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    Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma
    American Association for Cancer Research (AACR) ; 2021
    In:  Clinical Cancer Research Vol. 27, No. 4 ( 2021-02-15), p. 1048-1057
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 4 ( 2021-02-15), p. 1048-1057
    Abstract: VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma. Patients and Methods: Eighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A, n = 50) or pembrolizumab monotherapy (cohort B, n = 30). The primary endpoint was 6-month progression-free survival (PFS-6). Assessed biomarkers included evaluation of tumor programmed death-ligand 1 expression, tumor-infiltrating lymphocyte density, immune activation gene expression signature, and plasma cytokines. The neurologic assessment in neuro-oncology (NANO) scale was used to prospectively assess neurologic function. Results: Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% [95% confidence interval (CI), 16.3–41.5], median overall survival (OS) was 8.8 months (95% CI, 7.7–14.2), objective response rate (ORR) was 20%, and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI, 1.7–25.4), median OS was 10.3 months (95% CI, 8.5–12.5), and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased posttherapy plasma VEGF (cohort A) and mutant IDH1, unmethylated MGMT, and increased baseline PlGF and sVEGFR1 levels (cohort B). The NANO scale contributed to overall outcome assessment. Conclusions: Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in glioblastoma immunotherapy trials.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-20-2500
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 8
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    Abstract IA09: Single cell RNA-sequencing of circulating tumor cells
    American Association for Cancer Research (AACR) ; 2016
    In:  Clinical Cancer Research Vol. 22, No. 1_Supplement ( 2016-01-01), p. IA09-IA09
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 1_Supplement ( 2016-01-01), p. IA09-IA09
    Abstract: Isolation of circulating tumor cells (CTCs) in the blood allows noninvasive tumor sampling from patients with cancer. Molecular analysis of single CTCs may uncover heterogeneous cellular pathways that underlie disease progression and resistance to therapy. Using a microfluidic device, we isolated individual CTCs from patients with metastatic prostate cancer. Single candidate CTCs were micromanipulated after cell surface staining for epithelial (EpCAM) and mesenchymal (CDH11) markers, and then subjected to single cell RNA-sequencing. Digital gene expression profiles of lineage-confirmed CTCs were compared with each other, with primary prostate tumors, and with annotated markers of cellular signaling pathways. Single prostate CTCs displayed considerable heterogeneity in transcriptional profiles, but clustered according to patient of origin, indicating higher diversity in CTCs across different individuals (mean correlation 0.10 for CTCs within patients vs. 0.0014 for CTCs across patients, P=2.0x10E-11). Compared to primary tumors, CTCs were significantly enriched in 37 molecular pathways (FDR & lt;0.1), with the majority implicated in growth factor, cell adhesion, and hormone signaling. Gene mutations and alternative splice variants of the Androgen Receptor (AR) gene were rare in primary prostate tumors and CTCs from untreated patients, but were prevalent in patients with castration-resistant prostate cancer. Distinct AR variants, including AR-V7, were present within different cells of individual patients, as well as within individual CTCs. Together, single cell molecular analysis of human CTCs points to multiple mechanisms of drug resistance in advanced prostate cancer, and suggests the role of heterogeneous signaling pathways that cooperate with co-existing abnormalities in AR in mediating disease progression. Citation Format: David T. Miyamoto, Yu Zheng, Ben S. Wittner, Richard J. Lee, Huili Zhu, Katherine T. Broderick, Rushil Desai, Brian W. Brannigan, Kshitij S. Arora, Douglas M. Dahl, Lecia V. Sequist, Matthew R. Smith, Ravi Kapur, Chin-Lee Wu, Toshi Shioda, Sridhar Ramaswamy, David T. Ting, Mehmet Toner, Shyamala Maheswaran, Daniel A. Haber. Single cell RNA-sequencing of circulating tumor cells. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr IA09.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1557-3265.PMSCLINGEN15-IA09
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 9
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    Therapeutic Targeting of Mesothelin with Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia
    American Association for Cancer Research (AACR) ; 2021
    In:  Clinical Cancer Research Vol. 27, No. 20 ( 2021-10-15), p. 5718-5730
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 20 ( 2021-10-15), p. 5718-5730
    Abstract: We previously identified mesothelin (MSLN) as highly expressed in a significant fraction of acute myeloid leukemia (AML) but entirely silent in normal hematopoiesis, providing a promising antigen for immunotherapeutic targeting that avoids hematopoietic toxicity. Given that T cells genetically modified to express chimeric antigen receptors (CAR) are effective at eradicating relapsed/refractory acute lymphocytic leukemia, we developed MSLN-directed CAR T cells for preclinical evaluation in AML. Experimental Design: The variable light (VL) and heavy (VH) sequences from the MSLN-targeting SS1P immunotoxin were used to construct the single-chain variable fragment of the standard CAR containing 41-BB costimulatory and CD3Zeta stimulatory domains. The preclinical efficacy of MSLN CAR T cells was evaluated against AML cell lines and patient samples expressing various levels of MSLN in vitro and in vivo. Results: We demonstrate that MSLN is expressed on the cell surface of AML blasts and leukemic stem cell–enriched CD34+CD38− subset, but not on normal hematopoietic stem and progenitor cells (HSPC). We further establish that MSLN CAR T cells are highly effective in eliminating MSLN-positive AML cells in cell line– and patient-derived xenograft models. Importantly, MSLN CAR T cells can target and eradicate CD34+CD38− cells without impacting the viability of normal HSPCs. Finally, we show that CAR T-cell functionality can be improved by inhibition of the ADAM17 metalloprotease that promotes shedding of MSLN. Conclusions: These findings demonstrate that MSLN is a viable target for CAR T-cell therapy in AML and that inhibiting MSLN shedding is a promising approach to improve CAR T-cell efficacy.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-21-1546
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 10
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    Enhanced Fatty Acid Scavenging and Glycerophospholipid Metabolism Accompany Melanocyte Neoplasia Progression in Zebrafish
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 9 ( 2019-05-01), p. 2136-2151
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 9 ( 2019-05-01), p. 2136-2151
    Abstract: Alterations in lipid metabolism in cancer cells impact cell structure, signaling, and energy metabolism, making lipid metabolism a potential diagnostic marker and therapeutic target. In this study, we combined PET, desorption electrospray ionization-mass spectrometry (DESI-MS), nonimaging MS, and transcriptomic analyses to interrogate changes in lipid metabolism in a transgenic zebrafish model of oncogenic RAS-driven melanocyte neoplasia progression. Exogenous fatty acid uptake was detected in melanoma tumor nodules by PET using the palmitic acid surrogate tracer 14(R,S)-18F-fluoro-6-thia-heptadecanoic acid ([18F]-FTHA), consistent with upregulation of genes associated with fatty acid uptake found through microarray analysis. DESI-MS imaging revealed that FTHA uptake in tumors was heterogeneous. Transcriptome and lipidome analyses further highlighted dysregulation of glycerophospholipid pathways in melanoma tumor nodules, including increased abundance of phosphatidyl ethanolamine and phosphatidyl choline species, corroborated by DESI-MS, which again revealed heterogeneous phospholipid composition in tumors. Overexpression of the gene encoding lipoprotein lipase (LPL), which was upregulated in zebrafish melanocyte tumor nodules and expressed in the majority of human melanomas, accelerated progression of oncogenic RAS-driven melanocyte neoplasia in zebrafish. Depletion or antagonism of LPL suppressed human melanoma cell growth; this required simultaneous fatty acid synthase (FASN) inhibition when FASN expression was also elevated. Collectively, our findings implicate fatty acid acquisition as a possible therapeutic target in melanoma, and the methods we developed for monitoring fatty acid uptake have potential for diagnosis, patient stratification, and monitoring pharmacologic response. Significance: These findings demonstrate the translational potential of monitoring fatty acid uptake and identify lipoprotein lipase as a potential therapeutic target in melanoma.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-18-2409
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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