Hsp90 in Cancer: Beyond the Usual Suspects

Department of Cell and Molecular Pharmacology, Medical University of South Carolina, USA

Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC, USA

Luke Whitesell is a pediatric oncologist and senior research scientist at the Whitehead Institute. His clinical interests lie in the treatment of children with recurrent, refractory solid tumors. His laboratory efforts focus on the discovery and pre-clinical development of new anticancer drugs that target heat-shock proteins and the cellular heat-shock response. These ancient adaptive mechanisms act genome-wide to restore the normal protein folding environment within cells and enhance the survival of organisms under stress. In contrast to such well-recognized beneficial effects, however, they also enable cells to accommodate the drastic imbalances in signaling and profound alterations in DNA, protein and energy metabolism that occur in cancers. In essence, the malignant lifestyle confers a profound dependence on these “non-oncogenes”, strongly supporting the feasibility of targeting them to more effectively treat cancers. Building on these basic insights and the surprising ways in which HSP90 supports the evolution of new abilities in model organisms, a major goal of his current work is to test the idea that inhibiting HSP90 function can delay or prevent the evolution of a very undesirable trait in cancers, namely the acquisition of high level resistance to current chemotherapies.

Luke pursued graduate work in pharmacology at Cambridge University prior to completing medical training at Johns Hopkins University and residency at Boston Children’s Hospital. After fellowship training at the National Cancer Institute he joined the University of Arizona where he was Professor of Pediatric Oncology in the College of Medicine prior to taking his current position at the Whitehead Institute in Cambridge, MA.

Whitehead Institute for Biomedical Research, Cambridge, USA