We thank members of the Vander Heiden and Wolpin laboratories for discussions and the Koch Institute Swanson Biotechnology Center, particularly the Animal Imaging and Preclinical Testing Facility, for technical assistance. Major funding for this work was provided by the Lustgarten Foundation to B.M.W. and M.G.V.H. L.V.D. was supported by NIH Ruth Kirschstein Fellowship (F32CA210421). A.B. was supported by P50CA127003 and the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research. A.M. was supported by F32CA213810. E.C.L. was supported by the Damon Runyon Cancer Research Foundation (DRG-2299-17). A.N.L. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation (DRG-2241-15). B.M.W was supported by Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research, NIH/NCI (U01CA210171), Department of Defense (CA130288), Pancreatic Cancer Action Network, Stand Up To Cancer, Noble Effort Fund, Peter R. Leavitt Family Fund, Wexler Family Fund, and Promises for Purple. M.G.V.H. was supported in part by a Faculty Scholar grant from the Howard Hughes Medical Institute, and acknowledges additional funding from Stand Up To Cancer, The Ludwig Center at MIT, the Koch Institute Frontier Awards, the MIT Center for Precision Cancer Medicine, and the NIH (R01CA168653, P30CA14051).

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Nature thanks M. Löhr and the other anonymous reviewer(s) for their contribution to the peer review of this work.