Therapeutic Targets and Biomarkers Identified in Cancer Choline Phospholipid Metabolism

Abstract

Choline phospholipid metabolism is altered in a wide variety of cancers. The choline metabolite profile of tumors and cancer cells is characterized by an elevation of phosphocholine and total choline-containing compounds. Noninvasive magnetic resonance spectroscopy can be used to detect this elevation as an endogenous biomarker of cancer, or as a predictive biomarker for monitoring tumor response to novel targeted therapies. The enzymes directly causing this elevation, such as choline kinase, phospholipase C and phospholipase D may provide molecular targets for anticancer therapies. Signal transduction pathways that are activated in cancers, such as those mediated by the receptor tyrosine kinases breakpoint cluster region-abelson (Bcr-Abl), c-KIT or epidermal growth factor receptor (EGFR), correlate with the alterations in choline phospholipid metabolism of cancers, and also offer molecular targets for specific anticancer therapies. This review summarizes recently discovered molecular targets in choline phospholipid metabolism and signal transduction pathways, which may lead to novel anticancer therapies potentially being monitored by magnetic resonance spectroscopy techniques.

Keywords: :

• cancer
• choline
• inhibitor
• magnetic resonance spectroscopy
• metabolism
• pathway
• phospholipid
• signal transduction
• tyrosine kinase

Acknowledgements

NIH grant support was provided by R21 CA112216 (KG), P50 CA103175 (JHU ICMIC Program, KG), R21 CA108624 (NJS), and P30 CA046934 (UCHSC Cancer Center Core Grant, NJS).

Additional information

Funding

NIH grant support was provided by R21 CA112216 (KG), P50 CA103175 (JHU ICMIC Program, KG), R21 CA108624 (NJS), and P30 CA046934 (UCHSC Cancer Center Core Grant, NJS).