Grant: Undergraduate Student Research Awards (USRA)

Rearranged during transfection (RET) is a receptor tyrosine kinase that acts as an oncogene in multiple tumour types including those of the thyroid, lung and pancreas, and can also give rise to the inherited cancer syndrome multiple endocrine neoplasia 2. These cancers are frequently hard to treat, with targeted therapies being the most successful options. Currently, RET-selective kinase inhibitors can be used as therapies to treat these RET-associated tumours. However, acquired resistance to these drugs inevitably occurs and novel complementary therapeutic strategies need to be identified. Genetic synthetic dosage lethality (SDL) screens are a systematic approach that can help identify novel potential genes or pathways that contribute to RET-mediated cell growth which could be investigated as additional targets in cancer models. In our studies, loss of SDL genes, through gene knockdown methods, affects cell growth only when RET is over expressed or over active, but not in normal cells, suggesting that these genes could be targeted to complement inhibition of the RET kinase as alternative approaches for cancer therapy. In the proposed project, the student will use data generated in previous unbiased screens to explore possible SDL candidates and confirm their impact on RET-mediated cell growth.