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PMID: 19935796 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Metabolic assessment of the action of targeted cancer therapeutics using magnetic resonance spectroscopy.

British journal of cancer ·Vol. 102 ·No. 1 ·2010-01-05 ·Pages 1-7

Beloueche-Babari M, Chung YL, Al-Saffar NM, Falck-Miniotis M, Leach MO

Abstract

Developing rational targeted cancer drugs requires the implementation of pharmacodynamic (PD), preferably non-invasive, biomarkers to aid response assessment and patient follow-up. Magnetic resonance spectroscopy (MRS) allows the non-invasive study of tumour metabolism. We describe the MRS-detectable PD biomarkers resulting from the action of targeted therapeutics, and discuss their biological significance and future translation into clinical use.

MeSH Terms
Angiogenesis Inhibitors/pharmacology,therapeutic use Animals Antineoplastic Agents/pharmacology,therapeutic use Biomarkers Choline/metabolism Drug Delivery Systems Drug Monitoring/methods Energy Metabolism/drug effects Enzyme Inhibitors/pharmacology,therapeutic use Histone Deacetylases/metabolism Humans Magnetic Resonance Spectroscopy/methods Neoplasm Proteins/antagonists & inhibitors,metabolism Neoplasms/drug therapy,metabolism Phospholipids/metabolism Protein Kinases/metabolism Signal Transduction/drug effects Translational Research, Biomedical Tumor Cells, Cultured/drug effects,metabolism Xenograft Model Antitumor Assays
Chemicals
Angiogenesis Inhibitors Antineoplastic Agents Biomarkers Enzyme Inhibitors Neoplasm Proteins Phospholipids Protein Kinases Histone Deacetylases Choline
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Beloueche-Babari M
Section of Magnetic Resonance, Cancer Research UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK. mouniab@icr.ac.uk
Chung Y-L
Al-Saffar N M S
Falck-Miniotis M
Leach M O
References (47)
47 references, click to expand
  1. Ras inhibition in glioblastoma down-regulates hypoxia-inducible factor-1alpha, causing glycolysis shutdown and cell death.
    Cancer Res. 2005 Feb 1;65(3):999-1006 PMID: 15705901
  2. Magnetic resonance spectroscopy monitoring of mitogen-activated protein kinase signaling inhibition.
    Cancer Res. 2005 Apr 15;65(8):3356-63 PMID: 15833869
  3. Mechanism-based target identification and drug discovery in cancer research.
    Science. 2000 Mar 17;287(5460):1969-73 PMID: 10720316
  4. Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells.
    Cancer Res. 1999 Jan 1;59(1):80-4 PMID: 9892190
  5. Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy.
    Magn Reson Med. 2003 Feb;49(2):223-32 PMID: 12541241
  6. Detection of histone deacetylase inhibition by noninvasive magnetic resonance spectroscopy.
    Mol Cancer Ther. 2006 May;5(5):1325-34 PMID: 16731766
  7. Regulation of choline kinase activity by Ras proteins involves Ral-GDS and PI3K.
    Oncogene. 2002 Jan 31;21(6):937-46 PMID: 11840339
  8. Biomarkers in early clinical trials: the committed and the skeptics.
    Clin Cancer Res. 2008 Apr 15;14(8):2512; author reply 2513-4 PMID: 18413847
  9. Metabolite changes in HT-29 xenograft tumors following HIF-1alpha inhibition with PX-478 as studied by MR spectroscopy in vivo and ex vivo.
    NMR Biomed. 2005 Nov;18(7):430-9 PMID: 16206237
  10. SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth.
    Cell Metab. 2008 Sep;8(3):224-36 PMID: 18762023
  11. Peripheral zone prostate cancer in patients with elevated PSA levels and low free-to-total PSA ratio: detection with MR imaging and MR spectroscopy.
    Radiology. 2009 Oct;253(1):135-43 PMID: 19703854
  12. Phase II study of the antiangiogenic agent SU5416 in patients with advanced soft tissue sarcomas.
    Clin Cancer Res. 2004 Sep 1;10(17):5732-40 PMID: 15355900
  13. Magnetic resonance spectroscopy as an imaging tool for cancer: a review of the literature.
    J Am Osteopath Assoc. 2006 Jan;106(1):23-7 PMID: 16428685
  14. Increases in NMR-visible lipid and glycerophosphocholine during phenylbutyrate-induced apoptosis in human prostate cancer cells.
    Biochim Biophys Acta. 2005 May 1;1734(1):1-12 PMID: 15866478
  15. Neoadjuvant chemotherapy of locally advanced breast cancer: predicting response with in vivo (1)H MR spectroscopy--a pilot study at 4 T.
    Radiology. 2004 Nov;233(2):424-31 PMID: 15516615
  16. Identification of magnetic resonance detectable metabolic changes associated with inhibition of phosphoinositide 3-kinase signaling in human breast cancer cells.
    Mol Cancer Ther. 2006 Jan;5(1):187-96 PMID: 16432178
  17. A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy.
    Clin Cancer Res. 2003 Nov 1;9(14):5101-12 PMID: 14613987
  18. Metabolic changes detected by in vivo magnetic resonance studies of HEPA-1 wild-type tumors and tumors deficient in hypoxia-inducible factor-1beta (HIF-1beta): evidence of an anabolic role for the HIF-1 pathway.
    Cancer Res. 2002 Feb 1;62(3):688-95 PMID: 11830521
  19. International Workshop on Standardization in Clinical Magnetic Resonance Spectroscopy Measurements: proceedings and recommendations.
    Acad Radiol. 1994 Oct;1(2):171-86 PMID: 9419483
  20. Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells.
    Neoplasia. 2006 Sep;8(9):758-71 PMID: 16984733
  21. Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo (13)C MRS.
    Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E623-30 PMID: 12217878
  22. Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR-ABL-positive cells.
    Clin Cancer Res. 2009 May 15;15(10):3442-50 PMID: 19401345
  23. The c-Myc Oncoprotein Interacts with Bcr.
    Curr Biol. 2003 Mar 4;13(5):437-41 PMID: 12620195
  24. Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies.
    J Natl Cancer Inst. 2006 May 3;98(9):580-98 PMID: 16670384
  25. Choline kinase activation is a critical requirement for the proliferation of primary human mammary epithelial cells and breast tumor progression.
    Cancer Res. 2004 Sep 15;64(18):6732-9 PMID: 15374991
  26. Tumour phospholipid metabolism.
    NMR Biomed. 1999 Nov;12(7):413-39 PMID: 10654290
  27. Translating basic cancer research into new cancer therapeutics.
    Trends Mol Med. 2002;8(4 Suppl):S1-9 PMID: 11927279
  28. Measurements of human breast cancer using magnetic resonance spectroscopy: a review of clinical measurements and a report of localized 31P measurements of response to treatment.
    NMR Biomed. 1998 Nov;11(7):314-40 PMID: 9859939
  29. RNA interference-mediated choline kinase suppression in breast cancer cells induces differentiation and reduces proliferation.
    Cancer Res. 2005 Dec 1;65(23):11034-43 PMID: 16322253
  30. Magnetic resonance spectroscopic pharmacodynamic markers of the heat shock protein 90 inhibitor 17-allylamino,17-demethoxygeldanamycin (17AAG) in human colon cancer models.
    J Natl Cancer Inst. 2003 Nov 5;95(21):1624-33 PMID: 14600095
  31. Applications of magnetic resonance spectroscopy in radiotherapy treatment planning.
    Br J Radiol. 2006 Sep;79 Spec No 1:S16-26 PMID: 16980681
  32. Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of a novel histone deacetylase inhibitor, LAQ824, in human colon carcinoma cells and xenografts.
    Neoplasia. 2008 Apr;10(4):303-13 PMID: 18392140
  33. Mining the plasma proteome for cancer biomarkers.
    Nature. 2008 Apr 3;452(7187):571-9 PMID: 18385731
  34. Expanding the use of magnetic resonance in the assessment of tumor response to therapy: workshop report.
    Cancer Res. 2005 Aug 15;65(16):7041-4 PMID: 16103049
  35. Studies of human tumors by MRS: a review.
    NMR Biomed. 1992 Sep-Oct;5(5):303-24 PMID: 1333263
  36. Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells.
    Clin Cancer Res. 2004 Oct 1;10(19):6661-8 PMID: 15475456
  37. Evaluation of lactate as a 1H nuclear magnetic resonance spectroscopy index for noninvasive prediction and early detection of tumor response to radiation therapy in EMT6 tumors.
    Radiat Res. 1998 Jul;150(1):38-42 PMID: 9650600
  38. Fatty acid synthase inhibition results in a magnetic resonance-detectable drop in phosphocholine.
    Mol Cancer Ther. 2008 Aug;7(8):2556-65 PMID: 18723500
  39. Noninvasive magnetic resonance spectroscopic pharmacodynamic markers of the choline kinase inhibitor MN58b in human carcinoma models.
    Cancer Res. 2006 Jan 1;66(1):427-34 PMID: 16397258
  40. Molecular imaging and targeted therapies in oncology: new concepts in treatment response assessment. a collection of cases.
    Int J Oncol. 2008 Sep;33(3):443-52 PMID: 18695872
  41. In vivo 31P MR spectral patterns and reproducibility in cancer patients studied in a multi-institutional trial.
    NMR Biomed. 2006 Jun;19(4):504-12 PMID: 16763965
  42. Hypoxia regulates choline kinase expression through hypoxia-inducible factor-1 alpha signaling in a human prostate cancer model.
    Cancer Res. 2008 Jan 1;68(1):172-80 PMID: 18172309
  43. Activation of fatty acid synthesis during neoplastic transformation: role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase.
    Exp Cell Res. 2002 Sep 10;279(1):80-90 PMID: 12213216
  44. Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells.
    Br J Cancer. 2001 Mar 2;84(5):691-6 PMID: 11237392
  45. Glycolysis in cancer: a potential target for therapy.
    Int J Biochem Cell Biol. 2007;39(7-8):1358-66 PMID: 17499003
  46. Metabolic signatures associated with a NAD synthesis inhibitor-induced tumor apoptosis identified by 1H-decoupled-31P magnetic resonance spectroscopy.
    Clin Cancer Res. 2005 May 1;11(9):3503-13 PMID: 15867253
  47. Changes in choline metabolism as potential biomarkers of phospholipase C{gamma}1 inhibition in human prostate cancer cells.
    Mol Cancer Ther. 2009 May;8(5):1305-11 PMID: 19417158
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
DOI
10.1038/sj.bjc.6605457
Email
mouniab@icr.ac.uk
Published
2010-01-05
Epub
2009-00-24
Pages
1-7
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2813738
Subset
IM
Grants
Department of Health · C1060/A10334 · United Kingdom
Department of Health · C1060/6916 · United Kingdom
Medical Research Council · United Kingdom
Cancer Research UK · United Kingdom
External Links
PubMed source DOI: 10.1038/sj.bjc.6605457 PMC Full Text View journal details
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