Received: 16 November 2021
Accepted: 15 July 2022
We thank A. Maitra and J. Fleming for PDAC cell lines and E. Baldelli for assistance with RPPA analyses.
Funding: M.V.H. was supported by the Slomo and Cindy Silvian Foundation. G.A.H. was supported by National Institute of General Medical Sciences grant P20GM130457. L.M.C. was supported by NCI T32CA009156 and American Cancer Society PF-20-140-01–CDD. J.N.D. was supported by the Slomo and Cindy Silvian Foundation, NCI T32CA071341, and F30CA243253. A.M.W. was supported by a fellowship from the American Cancer Society (F-18-061). R.D.T. was supported by NCI T32CA009156. S.L.C. and E.F.P. were supported by NCI CA203657. Support was provided by grants from the NCI to A.D.C. and/or C.J.D. (CA42978, R01CA175747, R01CA223775, P50CA196510, U01CA199235, P01CA203657, and R35CA232113) and from the Pancreatic Cancer Action Network/AACR (15-90-25-DER).
Author contributions: M.V.H. and C.J.D. designed the experiments. M.V.H., G.A.H., A.M.W., J.H.C., K.M.H., A.D.C., and C.J.D. wrote the manuscript. M.V.H., G.A.H., A.S., M.P., L.M.C., J.M.D., R.D.T., L.L., and A.R.C. performed the experiments. J.N.D., C.M.G., J.H.C., and K.M.H. provided computational analyses. L.L., C.A.L., and D.M.S. provided key experimental reagents. E.F.P., S.L.C., K.M.H., D.M.S., N.U.R., C.A.L., A.D.C., and C.J.D. provided scientific guidance.
Competing interests: C.J.D. is an advisory board member for Anchiano Therapeutics, Boragen, Deciphera Pharmaceuticals, Mirati Therapeutics, Revolution Medicines, and SHY Therapeutics; has received research funding support from Boragen, Deciphera Pharmaceuticals, Mirati Therapeutics, and SpringWorks Therapeutics; and has consulted for Day One Biotherapeutics, Eli Lilly, Jazz Therapeutics, Ribometrix, Sanofi, and Turning Point Therapeutics. A.D.C. has consulted for Eli Lilly and Mirati Therapeutics. E.F.P. and M.P. are consultants for and receive royalties from Avant Diagnostics and TheraLink Technologies Inc. E.F.P. is a consultant to and shareholder of Avant Diagnostics Inc. and Perthera Inc. and received funding support from Mirati Therapeutics, Genentech Inc., and AbbVie Inc. The other authors declare they have no competing interests.
Data and materials availability: Plasmids generated for this study will be deposited into Addgene. The crystal structure of KRASQ61E has been deposited into the Protein Data Bank (PDB accession code 7LZ5). All other data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials.