Metabolite systems profiling identifies exploitable weaknesses in retinoblastoma

Swagatika Sahoo , Ranjith Kumar , Ravi Kumar , Brandon Nicolay , Omkar Mohite , Karthikeyan Sivaraman , Vikas Khetan , Pukhraj Rishi , Suganeswari Ganesan , Krishnakumar Subramanyan , Karthik Raman , Wayne Miles , Sailaja V. Elchuri , FEBS Letters (2018) .


Retinoblastoma (RB) is a childhood eye cancer. Currently, chemotherapy, local therapy, and enucleation are the main ways in which these tumors are managed. The present work is the first study that uses constraint-based reconstruction and analysis approaches to identify and explain RB-specific survival strategies, which are RB tumor specific. Importantly, our model-specific secretion profile is also found in RB1-depleted human retinal cells in vitro and suggests that novel biomarkers involved in lipid metabolism may be important. Finally, RB-specific synthetic lethals have been predicted as lipid and nucleoside transport proteins that can aid in novel drug target development.