New Hypotheses and Opportunities in Endocrine Therapy: Amplification of Oestrogen-induced Apoptosis

Overview

Journal Breast

Publisher Elsevier

Specialties Endocrinology
Oncology

Date 2009 Nov 17

PMID 19914527

Citations 15

Authors

V Craig Jordan

Joan S Lewis-Wambi

Roshani R Patel

Helen Kim

Eric A Ariazi

Affiliations

Soon will be listed here.

Abstract

Aims: To outline the progress being made in the understanding of acquired resistance to long term therapy with the selective oestrogen receptor modulators (SERMs, tamoxifen and raloxifene) and aromatase inhibitors. The question to be addressed is how we can amplify the new biology of oestrogen-induced apoptosis to create more complete responses in exhaustively antihormone treated metastatic breast cancer.

Methods And Results: Three questions are posed and addressed. (1) Do we know how oestrogen works? (2) Can we improve adjuvant antihormonal therapy? (3) Can we enhance oestrogen-induced apoptosis? The new player in oestrogen action is GPR30 and there are new drugs specific for this target to trigger apoptosis. Similarly, anti-angiogenic drugs can be integrated into adjuvant antihormone therapy or to enhance oestrogen-induced apoptosis in Phase II antihormone resistant breast cancer. The goal is to reduce the development of acquired antihormone resistance or undermine the resistance of breast cancer cells to undergo apoptosis with oestrogen respectively. Finally, drugs to reduce the synthesis of glutathione, a subcellular molecule compound associated with drug resistance, can enhance oestradiol-induced apoptosis.

Conclusions: We propose an integrated approach for the rapid testing of agents to blunt survival pathways and amplify oestrogen-induced apoptosis and tumour regression in Phase II resistant metastatic breast cancer. This Pharma platform will provide rapid clinical results to predict efficacy in large scale clinical trials.

Citing Articles

DNA Damage Responses in Tumors Are Not Proliferative Stimuli, but Rather They Are DNA Repair Actions Requiring Supportive Medical Care.

Suba Z Cancers (Basel). 2024; 16(8).

PMID: 38672654 PMC: 11049279. DOI: 10.3390/cancers16081573.

Enhanced IFNα Signaling Promotes Ligand-Independent Activation of ERα to Promote Aromatase Inhibitor Resistance in Breast Cancer.

Escher T, Dandawate P, Sayed A, Hagan C, Anant S, Lewis-Wambi J Cancers (Basel). 2021; 13(20).

PMID: 34680281 PMC: 8534010. DOI: 10.3390/cancers13205130.

Compensatory Estrogen Signal Is Capable of DNA Repair in Antiestrogen-Responsive Cancer Cells via Activating Mutations.

Suba Z J Oncol. 2020; 2020:5418365.

PMID: 32774370 PMC: 7407016. DOI: 10.1155/2020/5418365.

Interaction of the Anti-Proliferative GPER Inverse Agonist ERα17p with the Breast Cancer Cell Plasma Membrane: From Biophysics to Biology.

Trichet M, Lappano R, Belnou M, Salazar Vazquez L, Alves I, Ravault D Cells. 2020; 9(2).

PMID: 32075246 PMC: 7072814. DOI: 10.3390/cells9020447.

Carcinogenesis explained within the context of a theory of organisms.

Sonnenschein C, Soto A Prog Biophys Mol Biol. 2016; 122(1):70-76.

PMID: 27498170 PMC: 5501415. DOI: 10.1016/j.pbiomolbio.2016.07.004.

References

Jordan V, Allen K . Evaluation of the antitumour activity of the non-steroidal antioestrogen monohydroxytamoxifen in the DMBA-induced rat mammary carcinoma model. Eur J Cancer (1965). 1980; 16(2):239-51. DOI: 10.1016/0014-2964(80)90156-5. View

Swaby R, Jordan V . Low-dose estrogen therapy to reverse acquired antihormonal resistance in the treatment of breast cancer. Clin Breast Cancer. 2008; 8(2):124-33. DOI: 10.3816/CBC.2008.n.012. View

Helguero L, Faulds M, Gustafsson J, Haldosen L . Estrogen receptors alfa (ERalpha) and beta (ERbeta) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Oncogene. 2005; 24(44):6605-16. DOI: 10.1038/sj.onc.1208807. View

Jordan V . Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov. 2003; 2(3):205-13. DOI: 10.1038/nrd1031. View

Kennedy B . Hormone therapy for advanced breast cancer. Cancer. 1965; 18(12):1551-7. DOI: 10.1002/1097-0142(196512)18:12<1551::aid-cncr2820181206>3.0.co;2-1. View

Lewis J, Osipo C, Meeke K, Jordan V . Estrogen-induced apoptosis in a breast cancer model resistant to long-term estrogen withdrawal. J Steroid Biochem Mol Biol. 2005; 94(1-3):131-41. DOI: 10.1016/j.jsbmb.2004.12.032. View

Medina P, Goodin S . Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin Ther. 2008; 30(8):1426-47. DOI: 10.1016/j.clinthera.2008.08.008. View

Goetz M, Rae J, Suman V, Safgren S, Ames M, Visscher D . Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol. 2005; 23(36):9312-8. DOI: 10.1200/JCO.2005.03.3266. View

Lewis J, Cheng D, Jordan V . Targeting oestrogen to kill the cancer but not the patient. Br J Cancer. 2004; 90(5):944-9. PMC: 2409614. DOI: 10.1038/sj.bjc.6601627. View

10.

Boulay A, Rudloff J, Ye J, Zumstein-Mecker S, OReilly T, Evans D . Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res. 2005; 11(14):5319-28. DOI: 10.1158/1078-0432.CCR-04-2402. View

11.

Schnelldorfer T, Gansauge S, Gansauge F, Schlosser S, Beger H, Nussler A . Glutathione depletion causes cell growth inhibition and enhanced apoptosis in pancreatic cancer cells. Cancer. 2000; 89(7):1440-7. View

12.

Howell A, Dodwell D, Anderson H, Redford J . Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. Ann Oncol. 1992; 3(8):611-7. DOI: 10.1093/oxfordjournals.annonc.a058286. View

13.

Vogel V, Costantino J, Wickerham D, Cronin W, Cecchini R, Atkins J . Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA. 2006; 295(23):2727-41. DOI: 10.1001/jama.295.23.joc60074. View

14.

Jordan V . The rise of raloxifene and the fall of invasive breast cancer. J Natl Cancer Inst. 2008; 100(12):831-3. DOI: 10.1093/jnci/djn177. View

15.

Wolf D, Jordan V . A laboratory model to explain the survival advantage observed in patients taking adjuvant tamoxifen therapy. Recent Results Cancer Res. 1993; 127:23-33. DOI: 10.1007/978-3-642-84745-5_4. View

16.

Garrofe-Ochoa X, Melero-Fernandez de Mera R, Fernandez-Gomez F, Ribas J, Jordan J, Boix J . BAX and BAK proteins are required for cyclin-dependent kinase inhibitory drugs to cause apoptosis. Mol Cancer Ther. 2008; 7(12):3800-6. DOI: 10.1158/1535-7163.MCT-08-0655. View

17.

Martino S, Cauley J, Barrett-Connor E, Powles T, Mershon J, Disch D . Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 2004; 96(23):1751-61. DOI: 10.1093/jnci/djh319. View

18.

Ariazi E, Lewis-Wambi J, Gill S, Pyle J, Ariazi J, Kim H . Emerging principles for the development of resistance to antihormonal therapy: implications for the clinical utility of fulvestrant. J Steroid Biochem Mol Biol. 2006; 102(1-5):128-38. PMC: 1810511. DOI: 10.1016/j.jsbmb.2006.09.003. View

19.

Strom A, Hartman J, Foster J, Kietz S, Wimalasena J, Gustafsson J . Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D. Proc Natl Acad Sci U S A. 2004; 101(6):1566-71. PMC: 341775. DOI: 10.1073/pnas.0308319100. View

20.

Bailey H, Ripple G, Tutsch K, Arzoomanian R, Alberti D, Feierabend C . Phase I study of continuous-infusion L-S,R-buthionine sulfoximine with intravenous melphalan. J Natl Cancer Inst. 1997; 89(23):1789-96. DOI: 10.1093/jnci/89.23.1789. View