Why mTOR in Breast Cancer?
Why mTOR in Breast Cancer?
- Aberrant mTOR (mammalian target of rapamycin) activation has been observed in
breast cancer tumor samples1 - mTOR is an intracellular kinase that controls the production of proteins2,3
- mTOR is a central mediator of multiple signal transduction pathways
- mTOR regulates cell growth and proliferation, metabolism, and angiogenesis
- Important molecular changes in breast cancer affect mTOR activation and drug efficacy
- Mutations commonly found in breast cancer result in the dysregulation of mTOR activation1,4
- Resistance to standard anti-HER2 (human epidermal growth factor receptor-2) therapies for breast cancer may develop as a result of increased mTOR signaling5
Breast Cancer Background
- Breast cancer is the second most common cancer (after lung cancer), with approximately 1.15 million new cases diagnosed worldwide each year6
- In the United States, 192,730 new cases and 40,170 deaths are estimated for 20097
- mTOR is centrally located to influence the crosstalk between ER (estrogen receptor), EGFR (epidermal growth factor receptor), and HER28
- Aberrant mTOR activation as a result of signaling defects has been observed in breast cancer tumor samples1
- Breast cancer tumors are highly vascularized, and an increase in angiogenesis has been implicated in the development of breast cancer9
References
- Perez-Tenorio et al. Br J Cancer. 2002;86:540-545.
- Fingar et al. Mol Cell Biol. 2004;24:200-216.
- Wullschleger et al. Cell. 2006;124:471-484.
- Hynes and Boulay. J Mammary Gland Biol Neoplasia. 2006;11:53-61.
- Nahta et al. Breast Cancer Res. 2006;8:215.
- Parkin et al. CA Cancer J Clin. 2005;55:74-108.
- Surveillance, Epidemiology and End Results Web site. http://seer.cancer.gov.
- Johnston. Clin Cancer Res. 2005;11:889s-899s.
- Fox et al. Breast Cancer Res. 2007;9:216.