Selected publications

• Yuen John SP and Macaulay Valentine M (2008) Targeting the type 1 insulin-like growth factor receptor as a treatment for cancer. Expert Opin Ther Targets, 12(5):589-603.

• Chitnis Meenali M, Yuen John SP, Protheroe Andrew S, Pollak Michael, and Macaulay Valentine M (2008) The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res, 14(20):6364-70.

• Aleksic Tamara, Chitnis Meenali M, Perestenko Olga V, Gao Shan, Thomas Peter H, Turner Gareth D, Protheroe Andrew S, Howarth Mark, and Macaulay Valentine M (2010) Type 1 insulin-like growth factor receptor translocates to the nucleus of human tumor cells. Cancer Res, 70(16):6412-9.

• Yuen John SP, Akkaya Erdem, Wang Yong, Takiguchi Megumi, Peak Sandra, Sullivan Mark, Protheroe Andrew S, and Macaulay Valentine M (2009) Validation of the type 1 insulin-like growth factor receptor as a therapeutic target in renal cancer. Mol Cancer Ther, 8(6):1448-59.

• Turney B W, Turner G D, Brewster S F, and Macaulay V M (2010) Serial analysis of resected prostate cancer suggests up-regulation of type 1 IGF receptor with disease progression. BJU Int.

Val Macauley

Research goals

The aim of the IGF Group is to understand the role of insulin-like growth factor signaling in tumour biology, and to exploit this information in cancer therapy.

The type 1 IGF receptor (IGF-1R) mediates proliferation and cell survival, and is now recognized as an attractive cancer treatment target.  We are participating in early phase trials of IGF-1R inhibitors at the Oxford Cancer Centre, and plan further studies informed by our laboratory work.  We have shown that the IGF-1R is up-regulated in prostate and renal cancers, and is detectable in advanced primary tumours and metastatic disease.  We recently demonstrated that the IGF-1R undergoes ligand-dependent import into the nucleus of human tumour cells, and nuclear IGF-1R is associated with adverse prognosis in renal cancer (see Figure).  These findings suggest that nuclear IGF-1R translocation influences tumour biology, and we speculate that this phenomenon may have implications for therapy.  Our current work aims to identify factors that influence sensitivity to IGF-1R inhibitory drugs, and to guide design of rational combination treatments.

IGF-1R undergoes nuclear translocation.  Left: human prostate cancer cells show ligand-induced change in IGF-1R localization from predominantly membrane-associated signal in serum-starved cells, to punctate nuclear signal (arrows) in IGF-treated cells.  Right upper: nuclear IGF-1R in human clear cell renal cancer; lower: nuclear IGF-1R is associated with adverse survival in renal cancer.