Nikhil Wagle
Medical oncologist and cancer genomics researcher at Dana-Farber who studies why some patients respond exceptionally well to targeted drugs, including a patient whose tumour carried two activating MTOR mutations
Department of Medical Oncology and Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute; Brigham and Women's Hospital, Harvard Medical School (at the time of the study, 2014)
Most patients in early drug trials see little benefit, but now and then one patient responds far better than anyone else. Studying these 'exceptional responders' can reveal what makes a tumour sensitive. In WAG2014, Nikhil Wagle and colleagues sequenced the tumour of a patient who had an extraordinary response on a phase I trial of everolimus, an mTOR inhibitor, combined with pazopanib. The tumour carried two activating mutations in the MTOR gene itself at the same time, which made it dependent on mTOR and so vulnerable to everolimus. Because it is a single patient, the finding generates a hypothesis; it does not show that MTOR mutations predict response in general.
At the time of the study Wagle worked in the Department of Medical Oncology and the Center for Molecular Oncologic Pathology at Dana-Farber Cancer Institute and at Brigham and Women's Hospital, Harvard Medical School. An official current profile could not be opened for this batch, so later positions are not described here.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2014 | H | Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib WAG2014 First author: found two concurrent activating MTOR mutations in the tumour of a patient with an exceptional response to everolimus plus pazopanib. |
Co-authors in the Atlas 3
People with a profile here who share at least one study with Nikhil Wagle.
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- Brian C. Grabiner Catalogued cancer-associated MTOR mutations and showed that many of them hyperactivate the kinase and can predict sensitivity to rapamycin; he also contributed to the discovery of GATOR1
- David M. Sabatini Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Jonathan E. Rosenberg A bladder and urothelial cancer oncologist whose clinical trial work includes the case of an exceptional responder to everolimus with activating MTOR mutations.
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