William R. Sellers
Cancer biologist and physician-scientist whose work spans cancer genomics and cancer therapeutics, including how the PI3K/AKT/mTOR pathway drives tumours and how to target it.
Core Institute Member and Director of the Cancer Program, Broad Institute · Faculty, Harvard Medical School and Dana-Farber Cancer Institute · Formerly Vice President and Global Head of Oncology, Novartis Institutes for BioMedical Research
Sellers Lab, Cancer Program, Broad Institute of MIT and Harvard (Cambridge, Massachusetts, USA) ↗
Portrait: Broad Institute of MIT and Harvard
William Sellers is a physician-scientist who studies how cancers arise and how to treat them. His group at the Dana-Farber Cancer Institute in Boston was an early contributor to the idea that the PI3K/AKT pathway, which feeds into mTOR, is a major driver of tumours when it is switched on too strongly. Later he led oncology research at Novartis, and he now directs the Cancer Program at the Broad Institute.
The study in the Atlas, published in 2004 with Pradip Majumder as first author, used mice that carry an active form of the human AKT1 gene in the prostate. These mice develop early prostate changes that resemble a pre-cancer. Treating them with an mTOR inhibitor reversed the changes, which showed that growth driven by AKT depends on mTOR. The work also showed that the cells die by a mitochondrial route and that HIF-1 alpha targets, including glycolysis genes, respond to AKT and mTOR inhibition.
The paper also raised a caution for patients. If tumours switch on the survival gene BCL2 or increase HIF-1 alpha activity, they might escape mTOR inhibitors. That kind of resistance question is still relevant for cancer drugs aimed at this pathway.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2004 | A | mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways MAJ2004 Senior author: in mice with active AKT in the prostate, an mTOR inhibitor reversed the pre-cancerous change by triggering cell death and altering HIF-1 alpha-dependent metabolism. |
Co-authors in the Atlas 2
People with a profile here who share at least one study with William R. Sellers.
ShowHide
- James Brugarolas First author of the 2004 study showing that hypoxia switches off mTOR through REDD1 and the TSC1/TSC2 complex; now directs a kidney cancer research program studying signalling and resistance to targeted drugs.
- Pradip K. Majumder Cancer biologist who, in William Sellers's lab at Dana-Farber, showed that mTOR inhibitors reverse AKT-driven early prostate cancer in mice
Every researcher with a profile →
Thank you. That helps us know which pages have been read by someone who knows the work.
Thank you. We will check it and correct the page.
Thank you. Your answer was counted anonymously.