Metastatic disease remains the single most powerful predictor of adverse outcomes in Ewing sarcoma (ES) and other childhood sarcomas (malignant connective tissue tumours). High risk ES appears to be characterized by uninhibited outgrowth of neoplastic clones that have acquired additional genomic or epigenomic alterations, which facilitate the spread of the cancer cells.
Considerable research has focused on understanding the genetic and biomolecular alterations that underlie ES, including drug resistance. The challenge is to identify targetable events that can be used to characterize metastatic disease, which is widely held as an inefficient process, with only a tiny fraction of primary tumour cells surviving.
Emerging evidence suggests that a largely overlooked component of the spread of tumour cells is the impact of stress adaptation, occurring through acute changes in mRNA translation and protein synthesis. It is likely that specific ribonucleoprotein complexes known as stress granules (SG) are intimately connected to cancer biology, and even resistance to chemotherapy. However, targeting these structures in cancer cells has not been widely pursued. Dr. El-Naggar’s research will focus on understanding the link between stress granules and conditions that promote the spread of cancer cells.