Metabolomic prediction of treatment outcome in pancreatic ductal adenocarcinoma patients receiving gemcitabine

Phua, Lee Cheng; Goh, S. A.; Tai, David; Leow, Wei Qiang; Alkaff, Syed Muhammad Fahmy; Chan, Chung Yip; Kam, Juinn Huar; Lim, Tony Kiat Hon; Chan, Eric Chun Yong

doi:10.1007/s00280-017-3475-6

Cited by 27 publications

(16 citation statements)

References 39 publications

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“…In a prospective cohort study, dietary oleic acid intake was inversely related to the risk of pancreatic ductal adenocarcinoma (significant in patients with a BMI > 25 kg/m 2 ) [25]. Another study using tumor tissues of pancreatic ductal adenocarcinoma patients revealed that oleic acid and stearic acid were significantly higher in the group with favorable survival than in that with low survival [28]. Thus, our HFS might have provided additional benefits to the patients due to the high contents of oleic acid.…”

Section: Discussionmentioning

confidence: 99%

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients

et al. 2019

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We examined the effect of high fat oral nutritional supplement (HFS) on the nutritional status, oral intake, and serum metabolites of postoperative pancreaticobiliary cancer patients. Pancreaticobiliary cancer patients were voluntarily recruited. The HFS group received postoperative oral high fat supplementation (80% of total calories from fat; n = 12) until discharge; the control group (non-HFS; n = 9) received none. Dietary intake, anthropometry, blood chemistry, nutritional risk index (NRI), and serum metabolites analyzed by liquid chromatography tandem mass spectrometry were evaluated. Overall, cumulative caloric supply via parental and oral/enteral routes were not different between groups. However, oral fat intake, caloric intake, and NRI scores of the HFS group were higher than those of the non-HFS group with increased oral meal consumption. Oral caloric, fat, and meal intakes correlated with NRI scores. Metabolomics analysis identified 195 serum metabolites pre-discharge. Oral fat intake was correlated with 42 metabolites relevant to the glycerophospholipid pathway. Oral high fat-specific upregulation of sphingomyelin (d18:1/24:1), a previously reported pancreatic cancer-downregulated metabolite, and lysophosphatidylcholine (16:0) were associated with NRI scores. Provision of HFS in postoperative pancreatic cancer patients may facilitate the recovery of postoperative health status by increasing oral meal intake, improving nutritional status, and modulating serum metabolites

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Section: Discussionmentioning

confidence: 99%

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients

et al. 2019

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“…The study was designed to accurately exclude suspected pancreatic cancer in CP patients, with emphasis placed on optimizing the negative predictive value (NPV) [52,53]. In another metabolomic approach, Phua et al established metabotyping of resected PDAC tissue to predict gemcitabine treatment response in an adjuvant setting [54]. This proof-of-principle work showed that distinct tissue metabolomes, consisting of various amino acids, fatty acids, nucleobase intermediates and inorganic acids, could be used to depict the treatment response of gemcitabine [54].…”

Section: Opportunities Of Metabolic Profiles To Develop Targeted Thermentioning

confidence: 99%

“…In another metabolomic approach, Phua et al established metabotyping of resected PDAC tissue to predict gemcitabine treatment response in an adjuvant setting [54]. This proof-of-principle work showed that distinct tissue metabolomes, consisting of various amino acids, fatty acids, nucleobase intermediates and inorganic acids, could be used to depict the treatment response of gemcitabine [54]. The near future probably lies in a carefully selected panel of metabolome biomarkers that would allow for earlier diagnosis of PDAC, an easier determination of its stage and, ideally, provide indicators of prognosis or outcome.…”

Section: Opportunities Of Metabolic Profiles To Develop Targeted Thermentioning

confidence: 99%

Current Strategies and Future Perspectives for Precision Medicine in Pancreatic Cancer

Regel

Mayerle

Mahajan

2020

Cancers

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Current standard-of-care for patients with pancreatic ductal adenocarcinoma (PDAC) focusses on chemotherapeutic regimens and pancreatic cancer surgery. However, limited treatment options, late diagnosis in advanced tumor stages and the aggressive behavior of PDAC contribute to the high mortality of the disease. Consequently, there is an urgent need of precision medicine for pancreatic cancer patients. All over the world, numerous initiatives started in recent years to translate novel scientific discoveries into prospective clinical trials. One major approach pursues the stratification of PDAC patients according the tumor transcriptome to predict treatment response. Other strategies concentrate on genomic alterations and the identification of individualized targeted therapies. Further experimental studies are ongoing to detect novel biomarkers for cancer diagnosis, subtyping, treatment response prediction or clinical outcome. However, the challenge remains to transfer the knowledge into clinical practice. In this review, we summarize current literature and knowledge and highlight novel concepts of basic and clinical research uncovering suitable biomarkers and targeted therapies. Thus, we provide an overview of preclinical and clinical efforts of precision medicine in pancreatic cancer.

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“…Indeed, several lines of evidence indicate that metabolic flexibility is an important determinant of resistance to cancer therapies [ 25 ]. There is evidence from metabolomics analysis of tissue in pancreatic ductal adenocarcinoma patients that metabolic biomarkers may be predictive of resistance to the chemotherapy gemcitabine [ 26 ]. Metabolic changes may also be associated with drug-induced toxicity [ 27 , 28 ], suggesting that VOC biomarkers in breath could be explored as potential predictors of toxicity.…”

Section: Precision Medicine Applications For Breath Biopsymentioning

confidence: 99%

Breath biopsy for early detection and precision medicine in cancer

Schee

Pinheiro

Gaude

2018

ecancer

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Breath biopsy enables the non-invasive collection and analysis of volatile organic compounds (VOCs) in exhaled breath, providing valuable information about disease processes occurring in the body. Metabolic changes occur in cancer cells at the earliest stages of disease. We discuss progress in the use of breath biopsy for discovery of breath-based biomarkers for early detection of cancer, and potential applications for breath biopsy in enabling precision medicine in cancer.

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Metabolomic prediction of treatment outcome in pancreatic ductal adenocarcinoma patients receiving gemcitabine

Abstract: This work established proof-of-principle for GC/TOFMS-based global metabotyping of PDAC and laid the foundation for future discovery of metabolic biomarkers predictive of gemcitabine resistance in PDAC chemotherapy.

Cited by 27 publications

References 39 publications

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients

Current Strategies and Future Perspectives for Precision Medicine in Pancreatic Cancer

Breath biopsy for early detection and precision medicine in cancer

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