mTOR inhibitors in advanced breast cancer: ready for prime time?
- PMID: 23557794
- DOI: 10.1016/j.ctrv.2013.02.005
mTOR inhibitors in advanced breast cancer: ready for prime time?
Abstract
Current therapeutic approaches for advanced breast cancer frequently _target receptors mediating cell survival and proliferation, such as the estrogen receptor and/or progesterone receptor and human epidermal growth factor receptor-2. Although these approaches are effective for many patients, treatment resistance is common. Therefore, new treatment approaches are needed for patients with advanced breast cancer. Mammalian _target of rapamycin is a highly conserved serine-threonine kinase that acts as a major signaling hub that integrates and synergizes with cellular proliferation, survival, and/or motility signals mediated by estrogen receptor, human epidermal growth factor receptor-2, and other receptor tyrosine kinases. Dysregulation of mammalian _target of rapamycin signaling occurs in various tumor types, including breast cancer, and has been associated with cancer pathogenesis, disease progression, and treatment resistance. Recent clinical trials show that combined inhibition of mammalian _target of rapamycin and estrogen receptor represents an effective strategy for treating hormone receptor-positive advanced breast cancer progressing on nonsteroidal aromatase inhibitor therapy, and data from ongoing trials combining mammalian _target of rapamycin inhibition with human epidermal growth factor receptor-2-_targeted therapy are awaited. This review focuses on the molecular rationale underlying strategies to enhance sensitivity to treatment in hormone receptor-positive and human epidermal growth factor receptor-2-positive advanced breast cancer, the clinical efficacy of such approaches, and future perspectives.
Keywords: Advanced breast cancer; Endocrine resistance; Estrogen receptor; Everolimus; Exemestane; Human epidermal growth factor receptor-2; Progesterone receptor; mTOR inhibitor.
Copyright © 2013. Published by Elsevier Ltd.
Similar articles
-
The phosphoinositide-3-kinase-Akt-mTOR pathway as a therapeutic _target in breast cancer.J Natl Compr Canc Netw. 2013 Jun 1;11(6):670-8. doi: 10.6004/jnccn.2013.0086. J Natl Compr Canc Netw. 2013. PMID: 23744866 Free PMC article. Review.
-
Phosphatidylinositol 3-kinase/AKT/mammalian _target of rapamycin pathway inhibition: a breakthrough in the management of luminal (ER+/HER2-) breast cancers?Curr Opin Oncol. 2012 Nov;24(6):623-34. doi: 10.1097/CCO.0b013e328358a2b5. Curr Opin Oncol. 2012. PMID: 22960556 Review.
-
Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-_targeting mammalian _target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase.Breast Cancer Res. 2014 Sep 11;16(5):430. doi: 10.1186/s13058-014-0430-x. Breast Cancer Res. 2014. PMID: 25212826 Free PMC article.
-
The emergence of _targeted drugs in breast cancer to prevent resistance to endocrine treatment and chemotherapy.Expert Opin Pharmacother. 2014 Apr;15(5):681-700. doi: 10.1517/14656566.2014.885952. Epub 2014 Feb 28. Expert Opin Pharmacother. 2014. PMID: 24579888 Review.
-
A Phase II Open Label Study of Everolimus in Combination With Endocrine Therapy in Resistant Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer.Clin Breast Cancer. 2020 Apr;20(2):89-97. doi: 10.1016/j.clbc.2019.06.005. Epub 2019 Jun 26. Clin Breast Cancer. 2020. PMID: 31932237 Clinical Trial.
Cited by
-
The roles of macrophage autophagy in atherosclerosis.Acta Pharmacol Sin. 2016 Feb;37(2):150-6. doi: 10.1038/aps.2015.87. Epub 2016 Jan 11. Acta Pharmacol Sin. 2016. PMID: 26750103 Free PMC article. Review.
-
Pneumocystis jirovecii pneumonia following everolimus treatment of metastatic breast cancer.Med Mycol Case Rep. 2014 Sep 16;6:34-6. doi: 10.1016/j.mmcr.2014.08.007. eCollection 2014 Oct. Med Mycol Case Rep. 2014. PMID: 25379397 Free PMC article.
-
Genetic variants in the mTOR pathway and interaction with body size and weight gain on breast cancer risk in African-American and European American women.Cancer Causes Control. 2016 Aug;27(8):965-76. doi: 10.1007/s10552-016-0774-x. Epub 2016 Jun 17. Cancer Causes Control. 2016. PMID: 27314662 Free PMC article.
-
OncoRep: an n-of-1 reporting tool to support genome-guided treatment for breast cancer patients using RNA-sequencing.BMC Med Genomics. 2015 May 21;8:24. doi: 10.1186/s12920-015-0095-z. BMC Med Genomics. 2015. PMID: 25989980 Free PMC article.
-
Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase.J Cell Biol. 2020 Feb 3;219(2):e201905190. doi: 10.1083/jcb.201905190. J Cell Biol. 2020. PMID: 31819976 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous