Potential Options for Managing LOX+ ER- Breast Cancer Patients

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 May 6

PMID 27147578

Citations 5

Authors

Yong Han

Shenyi Lian

Xingran Cui

Kexin Meng

Balazs Gyorffy

Tao Jin

Dongsheng Huang

Affiliations

Soon will be listed here.

Abstract

Overexpression of lysyl oxidase (LOX) is often observed in estrogen receptor negative (ER-) breast cancer patients with bone metastasis. In the present bioinformatics study, we observed that LOX is a prognostic factor for poor progression free survival in patients with ER- breast cancer. LOX overexpression was positively correlated with resistance to radiation, doxorubin and mitoxantrone, but negatively correlated with resistance to bisphosphonate, PARP1 inhibitors, cisplatin, trabectedin and gemcitabine. LOX overexpression was also associated with EMT and stemness of cancer cells, which leads to chemotherapeutic resistance and poor outcome in ER- patients. Although we suggest several therapeutic interventions that may help in the management of LOX+ ER- breast cancer patients, experiments to validate the function of LOX in ER- breast cancer are still needed.

Citing Articles

Targeting Pivotal Hallmarks of Cancer for Enhanced Therapeutic Strategies in Triple-Negative Breast Cancer Treatment-In Vitro, In Vivo and Clinical Trials Literature Review.

Szulc A, Wozniak M Cancers (Basel). 2024; 16(8).

PMID: 38672570 PMC: 11047913. DOI: 10.3390/cancers16081483.

The Multifaceted Roles of Copper in Cancer: A Trace Metal Element with Dysregulated Metabolism, but Also a Target or a Bullet for Therapy.

Lelievre P, Sancey L, Coll J, Deniaud A, Busser B Cancers (Basel). 2020; 12(12).

PMID: 33271772 PMC: 7760327. DOI: 10.3390/cancers12123594.

ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis.

Shanbhag V, Jasmer-McDonald K, Zhu S, Martin A, Gudekar N, Khan A Proc Natl Acad Sci U S A. 2019; 116(14):6836-6841.

PMID: 30890638 PMC: 6452744. DOI: 10.1073/pnas.1817473116.

Silibinin Inhibits NSCLC Metastasis by Targeting the EGFR/LOX Pathway.

Hou X, Du H, Quan X, Shi L, Zhang Q, Wu Y Front Pharmacol. 2018; 9:21.

PMID: 29472856 PMC: 5809401. DOI: 10.3389/fphar.2018.00021.

Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines.

Karlic H, Haider F, Thaler R, Spitzer S, Klaushofer K, Varga F Int J Mol Sci. 2017; 18(9).

PMID: 28914765 PMC: 5618631. DOI: 10.3390/ijms18091982.

References

Nienhuis H, Arjaans M, Timmer-Bosscha H, de Vries E, Schroder C . Human stromal cells are required for an anti-breast cancer effect of zoledronic acid. Oncotarget. 2015; 6(27):24436-47. PMC: 4695196. DOI: 10.18632/oncotarget.4421. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Abdel-Fatah T, Arora A, Moseley P, Perry C, Rakha E, Green A . DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers. Oncotarget. 2015; 6(26):21964-78. PMC: 4673139. DOI: 10.18632/oncotarget.4157. View

Fan L, Strasser-Weippl K, Li J, St Louis J, Finkelstein D, Yu K . Breast cancer in China. Lancet Oncol. 2014; 15(7):e279-89. DOI: 10.1016/S1470-2045(13)70567-9. View

Hu X, Zhang J, Xu B, Cai L, Ragaz J, Wang Z . Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015; 16(4):436-46. DOI: 10.1016/S1470-2045(15)70064-1. View

Cox T, Rumney R, Schoof E, Perryman L, Hoye A, Agrawal A . The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature. 2015; 522(7554):106-110. PMC: 4961239. DOI: 10.1038/nature14492. View

Lehmann B, Bauer J, Chen X, Sanders M, Chakravarthy A, Shyr Y . Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011; 121(7):2750-67. PMC: 3127435. DOI: 10.1172/JCI45014. View

Davis A, Wiegers T, Johnson R, Lay J, Lennon-Hopkins K, Saraceni-Richards C . Text mining effectively scores and ranks the literature for improving chemical-gene-disease curation at the comparative toxicogenomics database. PLoS One. 2013; 8(4):e58201. PMC: 3629079. DOI: 10.1371/journal.pone.0058201. View

Tsai K, Li G, Chen C, Yeh M, Huang J, Tseng H . Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype. Breast Cancer Res Treat. 2015; 153(1):219-34. DOI: 10.1007/s10549-015-3525-x. View

10.

Feng J, Tang L . SPARC in Tumor Pathophysiology and as a Potential Therapeutic Target. Curr Pharm Des. 2014; 20(39):6182-90. DOI: 10.2174/1381612820666140619123255. View

11.

Liu Y, Zhu P, Wang Y, Wei Z, Tao L, Zhu Z . Antimetastatic Therapies of the Polysulfide Diallyl Trisulfide against Triple-Negative Breast Cancer (TNBC) via Suppressing MMP2/9 by Blocking NF-κB and ERK/MAPK Signaling Pathways. PLoS One. 2015; 10(4):e0123781. PMC: 4415928. DOI: 10.1371/journal.pone.0123781. View

12.

Nagai M, Gerhard R, Fregnani J, Nonogaki S, Rierger R, Netto M . Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients. Breast Cancer Res Treat. 2010; 126(1):1-14. DOI: 10.1007/s10549-010-0867-2. View

13.

Livraghi L, Garber J . PARP inhibitors in the management of breast cancer: current data and future prospects. BMC Med. 2015; 13:188. PMC: 4535298. DOI: 10.1186/s12916-015-0425-1. View

14.

Tichet M, Prodhomme V, Fenouille N, Ambrosetti D, Mallavialle A, Cerezo M . Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis. Nat Commun. 2015; 6:6993. DOI: 10.1038/ncomms7993. View

15.

DeSantis C, Ma J, Bryan L, Jemal A . Breast cancer statistics, 2013. CA Cancer J Clin. 2013; 64(1):52-62. DOI: 10.3322/caac.21203. View

16.

Andreopoulou E, Schweber S, Sparano J, McDaid H . Therapies for triple negative breast cancer. Expert Opin Pharmacother. 2015; 16(7):983-98. PMC: 5995333. DOI: 10.1517/14656566.2015.1032246. View

17.

Odri G, Kim P, Lamoureux F, Charrier C, Battaglia S, Amiaud J . Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing's sarcoma via inhibition of cell migration. BMC Cancer. 2014; 14:169. PMC: 3975287. DOI: 10.1186/1471-2407-14-169. View

18.

Ichinose Y, Migita K, Nakashima T, Kawakami A, Aoyagi T, Eguchi K . Effects of bisphosphonate on the release of MMP-2 from cultured human osteoblasts. Tohoku J Exp Med. 2001; 192(2):111-8. DOI: 10.1620/tjem.192.111. View

19.

OShaughnessy J, Osborne C, Pippen J, Yoffe M, Patt D, Rocha C . Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med. 2011; 364(3):205-14. DOI: 10.1056/NEJMoa1011418. View

20.

Ruiz L, Baez-Vega P, Ruiz A, Peterse D, Monteiro J, Bracero N . Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis. Reprod Sci. 2015; 22(12):1496-508. PMC: 5933196. DOI: 10.1177/1933719115585144. View