Top

Breast Cancer Research

Published in:

Open Access 01-08-2014 | Research article

A joint analysis of metabolomics and genetics of breast cancer

Authors: Xiaohu Tang, Chao-Chieh Lin, Ivan Spasojevic, Edwin S Iversen, Jen-Tsan Chi, Jeffrey R Marks

Published in: Breast Cancer Research | Issue 4/2014

Abstract

Introduction

Remodeling of cellular metabolism appears to be a consequence and possibly a cause of oncogenic transformation in human cancers. Specific aspects of altered tumor metabolism may be amenable to therapeutic intervention and could be coordinated with other targeted therapies. In breast cancer, the genetic landscape has been defined most comprehensively in efforts such as The Cancer Genome Atlas (TCGA). However, little is known about how alterations of tumor metabolism correlate with this landscape.

Methods

In total 25 cancers (23 fully analyzed by TCGA) and 5 normal breast specimens were analyzed by gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry, quantitating 399 identifiable metabolites.

Results

We found strong differences correlated with hormone receptor status with 18% of the metabolites elevated in estrogen receptor negative (ER-) cancers compared to estrogen receptor positive (ER+) including many glycolytic and glycogenolytic intermediates consistent with increased Warburg effects. Glutathione (GSH) pathway components were also elevated in ER- tumors consistent with an increased requirement for handling higher levels of oxidative stress. Additionally, ER- tumors had high levels of the oncometabolite 2-hydroxyglutarate (2-HG) and the immunomodulatory tryptophan metabolite kynurenine. Kynurenine levels were correlated with the expression of tryptophan-degrading enzyme (IDO1). However, high levels of 2-HG were not associated with somatic mutations or expression levels of IDH1 or IDH2. BRCA1 mRNA levels were positively associated with coenzyme A, acetyl coenzyme A, and GSH and negatively associated with multiple lipid species, supporting the regulation of ACC1 and NRF2 by BRCA1. Different driver mutations were associated with distinct patterns of specific metabolites, such as lower levels of several lipid-glycerophosphocholines in tumors with mutated TP53. A strong metabolomic signature associated with proliferation rate was also observed; the metabolites in this signature overlap broadly with metabolites that define ER status as receptor status and proliferation rate were correlated.

Conclusions

The addition of metabolomic profiles to the public domain TCGA dataset provides an important new tool for discovery and hypothesis testing of the genetic regulation of tumor metabolism. Particular sets of metabolites may reveal insights into the metabolic dysregulation that underlie the heterogeneity of breast cancer.

Available only for authorised users

Comprehensive molecular portraits of human breast tumours. Nature. 2012, 490: 61-70. 10.1038/nature11412.

Levine AJ, Puzio-Kuter AM: The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010, 330: 1340-1344. 10.1126/science.1193494.CrossRefPubMed

Reitman ZJ, Jin G, Karoly ED, Spasojevic I, Yang J, Kinzler KW, He Y, Bigner DD, Vogelstein B, Yan H: Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc Natl Acad Sci U S A. 2011, 108: 3270-3275. 10.1073/pnas.1019393108.CrossRefPubMedPubMedCentral

Yuneva MO, Fan TW, Allen TD, Higashi RM, Ferraris DV, Tsukamoto T, Mates JM, Alonso FJ, Wang C, Seo Y, Chen X, Bishop JM: The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 2012, 15: 157-170. 10.1016/j.cmet.2011.12.015.CrossRefPubMedPubMedCentral

Maddocks OD, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH: Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2013, 493: 542-546. 10.1038/nature11743.CrossRefPubMed

Garcia-Cao I, Song MS, Hobbs RM, Laurent G, Giorgi C, de Boer VC, Anastasiou D, Ito K, Sasaki AT, Rameh L, Carracedo A, Vander Heiden MG, Cantley LC, Pinton P, Haigis MC, Pandolfi PP: Systemic elevation of PTEN induces a tumor-suppressive metabolic state. Cell. 2012, 149: 49-62. 10.1016/j.cell.2012.02.030.CrossRefPubMedPubMedCentral

Gatza ML, Kung HN, Blackwell KL, Dewhirst MW, Marks JR, Chi JT: Analysis of tumor environmental response and oncogenic pathway activation identifies distinct basal and luminal features in HER2-related breast tumor subtypes. Breast Cancer Res. 2011, 13: R62-10.1186/bcr2899.CrossRefPubMedPubMedCentral

Palaskas N, Larson SM, Schultz N, Komisopoulou E, Wong J, Rohle D, Campos C, Yannuzzi N, Osborne JR, Linkov I, Kastenhuber ER, Taschereau R, Plaisier SB, Tran C, Heguy A, Wu H, Sander C, Phelps ME, Brennan C, Port E, Huse JT, Graeber TG, Mellinghoff IK: 18 F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers. Cancer Res. 2011, 71: 5164-5174. 10.1158/0008-5472.CAN-10-4633.CrossRefPubMedPubMedCentral

Brauer HA, Makowski L, Hoadley KA, Casbas-Hernandez P, Lang LJ, Roman-Perez E, D’Arcy M, Freemerman AJ, Perou CM, Troester MA: Impact of tumor microenvironment and epithelial phenotypes on metabolism in breast cancer. Clin Cancer Res. 2013, 19: 571-585. 10.1158/1078-0432.CCR-12-2123.CrossRefPubMed

10.

Jerby L, Wolf L, Denkert C, Stein GY, Hilvo M, Oresic M, Geiger T, Ruppin E: Metabolic associations of reduced proliferation and oxidative stress in advanced breast cancer. Cancer Res. 2012, 72: 5712-5720. 10.1158/0008-5472.CAN-12-2215.CrossRefPubMed

11.

Kung HN, Marks JR, Chi JT: Glutamine synthetase is a genetic determinant of cell type-specific glutamine independence in breast epithelia. PLoS Genet. 2011, 7: e1002229-10.1371/journal.pgen.1002229.CrossRefPubMedPubMedCentral

12.

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Aksien LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406: 747-752. 10.1038/35021093.CrossRefPubMed

13.

Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, Feleppa F, Huschtscha LI, Thorne HJ, Fox SB, Yan M, French JD, Brown MA, Smyth GK, Visvader JE, Lindeman GJ: Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med. 2009, 15: 907-913. 10.1038/nm.2000.CrossRefPubMed

14.

Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K: Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11: 259-273. 10.1016/j.ccr.2007.01.013.CrossRefPubMed

15.

Sitter B, Lundgren S, Bathen TF, Halgunset J, Fjosne HE, Gribbestad IS: Comparison of HR MAS MR spectroscopic profiles of breast cancer tissue with clinical parameters. NMR Biomed. 2006, 19: 30-40. 10.1002/nbm.992.CrossRefPubMed

16.

Budczies J, Denkert C, Muller BM, Brockmoller SF, Klauschen F, Gyorffy B, Dietel M, Richter-Ehrenstein C, Marten U, Salek RM, Griffin JL, Hilvo M, Oresic M, Wohlgemuth G, Fiehn O: Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study. BMC Genomics. 2012, 13: 334-10.1186/1471-2164-13-334.CrossRefPubMedPubMedCentral

17.

Borgan E, Sitter B, Lingjaerde OC, Johnsen H, Lundgren S, Bathen TF, Sorlie T, Borresen-Dale AL, Gribbestad IS: Merging transcriptomics and metabolomics–advances in breast cancer profiling. BMC Cancer. 2010, 10: 628-10.1186/1471-2407-10-628.CrossRefPubMedPubMedCentral

18.

Hilvo M, Denkert C, Lehtinen L, Muller B, Brockmoller S, Seppanen-Laakso T, Budczies J, Bucher E, Yetukuri L, Castillo S, Berg E, Nygren H, Sysi-Aho M, Griffin JL, Fiehn O, Loibl S, Richter-Ehrenstein C, Radke C, Hyotylainen T, Kallioniemi O, Iljin K, Oresic M: Novel theranostic opportunities offered by characterization of altered membrane lipid metabolism in breast cancer progression. Cancer Res. 2011, 71: 3236-3245. 10.1158/0008-5472.CAN-10-3894.CrossRefPubMed

19.

Struys EA, Jansen EE, Verhoeven NM, Jakobs C: Measurement of urinary D- and L-2-hydroxyglutarate enantiomers by stable-isotope-dilution liquid chromatography-tandem mass spectrometry after derivatization with diacetyl-L-tartaric anhydride. Clin Chem. 2004, 50: 1391-1395. 10.1373/clinchem.2004.033399.CrossRefPubMed

20.

Storey JD, Tibshirani R: Statistical significance for genomewide studies. Proc Natl Acad Sci U S A. 2003, 100: 9440-9445. 10.1073/pnas.1530509100.CrossRefPubMedPubMedCentral

21.

Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998, 95: 14863-14868. 10.1073/pnas.95.25.14863.CrossRefPubMedPubMedCentral

22.

Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001, 98: 5116-5121. 10.1073/pnas.091062498.CrossRefPubMedPubMedCentral

23.

The Cancer Genome Atlas - data portal. [], [https://tcga-data.nci.nih.gov/tcga/]

24.

cBioPortal for Cancer Genomics. [], [http://www.cbioportal.org/public-portal/]

25.

Chia SK, Bramwell VH, Tu D, Shepherd LE, Jiang S, Vickery T, Mardis E, Leung S, Ung K, Pritchard KI, Parker JS, Bernard PS, Perou CM, Ellis MJ, Nielsen TO: A 50-gene intrinsic subtype classifier for prognosis and prediction of benefit from adjuvant tamoxifen. Clin Cancer Res. 2012, 18: 4465-4472. 10.1158/1078-0432.CCR-12-0286.CrossRefPubMedPubMedCentral

26.

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98: 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral

27.

Terunuma A, Putluri N, Mishra P, Mathe EA, Dorsey TH, Yi M, Wallace TA, Issaq HJ, Zhou M, Killian JK, Stevenson HS, Karoly ED, Chan K, Samanta S, Prieto D, Hsu TY, Kurley SJ, Putluri V, Sonavane R, Edelman DC, Wulff J, Starks AM, Yang Y, Kittles RA, Yfantis HG, Lee DH, Ioffe OB, Schiff R, Stephens RM, Meltzer PS, et al: MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis. J Clin Invest. 2014, 124: 398-412. 10.1172/JCI71180.CrossRefPubMed

28.

Griffith OW, Bridges RJ, Meister A: Transport of gamma-glutamyl amino acids: role of glutathione and gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1979, 76: 6319-6322. 10.1073/pnas.76.12.6319.CrossRefPubMedPubMedCentral

29.

Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, Marks KM, Prins RM, Ward PS, Yen KE, Liau LM, Rabinowitz JD, Cantley LC, Thompson CB, Vander Heiden MG, Su SM: Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009, 462: 739-744. 10.1038/nature08617.CrossRefPubMedPubMedCentral

30.

Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, Tsoi J, Clark O, Oldrini B, Komisopoulou E, Kunii K, Pedraza A, Schalm S, Silverman L, Miller A, Wang F, Yang H, Chen Y, Kernytsky A, Rosenblum MK, Liu W, Biller SA, Su SM, Brennan CW, Chan TA, Graeber TG, Yen KE, Mellinghoff IK: An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science. 2013, 340: 626-630. 10.1126/science.1236062.CrossRefPubMedPubMedCentral

31.

Moreau K, Dizin E, Ray H, Luquain C, Lefai E, Foufelle F, Billaud M, Lenoir GM, Venezia ND: BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase. J Biol Chem. 2006, 281: 3172-3181. 10.1074/jbc.M504652200.CrossRefPubMed

32.

Singh KK, Shukla PC, Yanagawa B, Quan A, Lovren F, Pan Y, Wagg CS, Teoh H, Lopaschuk GD, Verma S: Regulating cardiac energy metabolism and bioenergetics by targeting the DNA damage repair protein BRCA1. J Thorac Cardiovasc Surg. 2013, 146: 702-709. 10.1016/j.jtcvs.2012.12.046.CrossRefPubMed

33.

Bae I, Fan S, Meng Q, Rih JK, Kim HJ, Kang HJ, Xu J, Goldberg ID, Jaiswal AK, Rosen EM: BRCA1 induces antioxidant gene expression and resistance to oxidative stress. Cancer Res. 2004, 64: 7893-7909. 10.1158/0008-5472.CAN-04-1119.CrossRefPubMed

34.

Fan S, Meng Q, Saha T, Sarkar FH, Rosen EM: Low concentrations of diindolylmethane, a metabolite of indole-3-carbinol, protect against oxidative stress in a BRCA1-dependent manner. Cancer Res. 2009, 69: 6083-6091. 10.1158/0008-5472.CAN-08-3309.CrossRefPubMedPubMedCentral

35.

Gorrini C, Baniasadi PS, Harris IS, Silvester J, Inoue S, Snow B, Joshi PA, Wakeham A, Molyneux SD, Martin B, Bouwman P, Cescon DW, Elia AJ, Winterton-Perks Z, Cruickshank J, Brenner D, Tseng A, Musgrave M, Berman HK, Khokha R, Jonkers J, Mak TW, Gauthier ML: BRCA1 interacts with Nrf2 to regulate antioxidant signaling and cell survival. J Exp Med. 2013, 210: 1529-1544. 10.1084/jem.20121337.CrossRefPubMedPubMedCentral

36.

Cook RM, Franklin WA, Moore MD, Johnson BE, Miller YE: Mutational inactivation of aminoacylase-I in a small cell lung cancer cell line. Genes Chromosomes Cancer. 1998, 21: 320-325. 10.1002/(SICI)1098-2264(199804)21:4<320::AID-GCC5>3.0.CO;2-0.CrossRefPubMed

37.

Zhong Y, Onuki J, Yamasaki T, Ogawa O, Akatsuka S, Toyokuni S: Genome-wide analysis identifies a tumor suppressor role for aminoacylase 1 in iron-induced rat renal cell carcinoma. Carcinogenesis. 2009, 30: 158-164. 10.1093/carcin/bgn255.CrossRefPubMed

38.

Yasui M, Suenaga E, Koyama N, Masutani C, Hanaoka F, Gruz P, Shibutani S, Nohmi T, Hayashi M, Honma M: Miscoding properties of 2′-deoxyinosine, a nitric oxide-derived DNA Adduct, during translesion synthesis catalyzed by human DNA polymerases. J Mol Biol. 2008, 377: 1015-1023. 10.1016/j.jmb.2008.01.033.CrossRefPubMed

39.

Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009, 457: 910-914. 10.1038/nature07762.CrossRefPubMedPubMedCentral

40.

Chinnaiyan P, Kensicki E, Bloom G, Prabhu A, Sarcar B, Kahali S, Eschrich S, Qu X, Forsyth P, Gillies R: The metabolomic signature of malignant glioma reflects accelerated anabolic metabolism. Cancer Res. 2012, 72: 5878-5888. 10.1158/0008-5472.CAN-12-1572-T.CrossRefPubMedPubMedCentral

41.

Hitosugi T, Zhou L, Elf S, Fan J, Kang HB, Seo JH, Shan C, Dai Q, Zhang L, Xie J, Gu TL, Jin P, Aleckovic M, LeRoy G, Kang Y, Sudderth JA, DeBerardinis RJ, Luan CH, Chen GZ, Muller S, Shin DM, Owonikoko TK, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Ye K, Boggon TJ, Kang S, et al: Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell. 2012, 22: 585-600. 10.1016/j.ccr.2012.09.020.CrossRefPubMedPubMedCentral

42.

Platten M, Wick W, Van den Eynde BJ: Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012, 72: 5435-5440. 10.1158/0008-5472.CAN-12-0569.CrossRefPubMed

43.

Suzuki Y, Suda T, Furuhashi K, Suzuki M, Fujie M, Hahimoto D, Nakamura Y, Inui N, Nakamura H, Chida K: Increased serum kynurenine/tryptophan ratio correlates with disease progression in lung cancer. Lung Cancer. 2010, 67: 361-365. 10.1016/j.lungcan.2009.05.001.CrossRefPubMed

44.

Lyon DE, Walter JM, Starkweather AR, Schubert CM, McCain NL: Tryptophan degradation in women with breast cancer: a pilot study. BMC Res Notes. 2011, 4: 156-10.1186/1756-0500-4-156.CrossRefPubMedPubMedCentral

45.

Wang Z, Chatterjee D, Jeon HY, Akerman M, Vander Heiden MG, Cantley LC, Krainer AR: Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons. J Mol Cell Biol. 2012, 4: 79-87. 10.1093/jmcb/mjr030.CrossRefPubMed

46.

Kim S, Kim Do H, Jung WH, Koo JS: Metabolic phenotypes in triple-negative breast cancer. Tumour Biol. 2013, 34: 1699-1712. 10.1007/s13277-013-0707-1.CrossRefPubMed

47.

Dang CV: MYC, metabolism, cell growth, and tumorigenesis. Cold Spring Harb Perspect Med. 2013, 3: 1-15.CrossRef

48.

Freed-Pastor WA, Mizuno H, Zhao X, Langerod A, Moon SH, Rodriguez-Barrueco R, Barsotti A, Chicas A, Li W, Polotskaia A, Bissell MJ, Osborne TF, Tian B, Lowe SW, Silva JM, Borresen-Dale AL, Levine AJ, Bargonetti J, Prives C: Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway. Cell. 2012, 148: 244-258. 10.1016/j.cell.2011.12.017.CrossRefPubMedPubMedCentral

49.

Foster R, Griffin S, Grooby S, Feltell R, Christopherson C, Chang M, Sninsky J, Kwok S, Torrance C: Multiple metabolic alterations exist in mutant PI3K cancers, but only glucose is essential as a nutrient source. PLoS One. 2012, 7: e45061-10.1371/journal.pone.0045061.CrossRefPubMedPubMedCentral

50.

Aboagye EO, Bhujwalla ZM: Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res. 1999, 59: 80-84.PubMed

51.

Iorio E, Mezzanzanica D, Alberti P, Spadaro F, Ramoni C, D’Ascenzo S, Millimaggi D, Pavan A, Dolo V, Canevari S, Podo F: Alterations of choline phospholipid metabolism in ovarian tumor progression. Cancer Res. 2005, 65: 9369-9376. 10.1158/0008-5472.CAN-05-1146.CrossRefPubMed

52.

Zhang XH, Zhao C, Seleznev K, Song K, Manfredi JJ, Ma ZA: Disruption of G1-phase phospholipid turnover by inhibition of Ca2 + −independent phospholipase A2 induces a p53-dependent cell-cycle arrest in G1 phase. J Cell Sci. 2006, 119: 1005-1015. 10.1242/jcs.02821.CrossRefPubMedPubMedCentral

53.

Goldstein I, Rotter V: Regulation of lipid metabolism by p53 - fighting two villains with one sword. Trends Endocrinol Metab. 2012, 23: 567-575. 10.1016/j.tem.2012.06.007.CrossRefPubMed

54.

Li CH, Cheng YW, Liao PL, Kang JJ: Translocation of p53 to mitochondria is regulated by its lipid binding property to anionic phospholipids and it participates in cell death control. Neoplasia. 2010, 12: 150-160.CrossRefPubMedPubMedCentral

55.

He H, Conrad CA, Nilsson CL, Ji Y, Schaub TM, Marshall AG, Emmett MR: Method for lipidomic analysis: p53 expression modulation of sulfatide, ganglioside, and phospholipid composition of U87 MG glioblastoma cells. Anal Chem. 2007, 79: 8423-8430. 10.1021/ac071413m.CrossRefPubMed

56.

Listinsky JJ, Siegal GP, Listinsky CM: The emerging importance of alpha-L-fucose in human breast cancer: a review. Am J Transl Res. 2011, 3: 292-322.PubMedPubMedCentral

57.

Luporsi E, Andre F, Spyratos F, Martin PM, Jacquemier J, Penault-Llorca F, Tubiana-Mathieu N, Sigal-Zafrani B, Arnould L, Gompel A, Egele C, Poulet B, Clough KB, Crouet H, Fourquet A, Lefranc JP, Mathelin C, Rouyer N, Serin D, Spielmann M, Haugh M, Chenard MP, Brain E, de Cremoux P, Bellocq JP: Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. Breast Cancer Res Treat. 2012, 132: 895-915. 10.1007/s10549-011-1837-z.CrossRefPubMed

58.

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004, 351: 2817-2826. 10.1056/NEJMoa041588.CrossRefPubMed

Title: A joint analysis of metabolomics and genetics of breast cancer
Authors: Xiaohu Tang
Chao-Chieh Lin
Ivan Spasojevic
Edwin S Iversen
Jen-Tsan Chi
Jeffrey R Marks
Publication date: 01-08-2014
Publisher: BioMed Central
Published in: Breast Cancer Research / Issue 4/2014
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-014-0415-9

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2014

Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study

uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies

Mammographic features associated with interval breast cancers in screening programs

Dual HER2 blockade: preclinical and clinical data

The dynamic range of circulating tumor DNA in metastatic breast cancer

Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ

Keynote webinar | Spotlight on antibody–drug conjugates in cancer