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Objective: The goal of this study was to assess predictive factors for receiving interviews and matching in general surgery (GS), cardiothoracic surgery (TS), vascular surgery (VS), and plastic surgery (PS)., Design: The Texas Seeking Transparency in Applications to Residency (STAR) survey was analyzed for match years 2018-2023. Chi-Square Tests of Independence were used to assess differences among participants who received ≥16 vs <16 interviews and, separately, participants who matched vs went unmatched. Odds ratios (OR) for matching were adjusted for board scores, home region, publications, and honors in applicant specialty., Setting: All US medical schools participating in the Texas STAR survey from 2018-2023., Participants: All fourth-year students who completed the survey during the study period., Results: Of the 2,687 individuals included, 78.15% applied in GS, 13.58% in PS, 4.43% in VS, and 3.82% in TS. Participants had higher odds of receiving ≥16 interviews when having >240 step 1 score vs ≤239 (OR 1.76 (95% CI 1.46-2.12); p < 0.001), >250 step 2 score vs ≤249 (2.42 (2.00-2.91); p < 0.001), honors in their specialty (1.48 (1.21-1.80); p < 0.001), and >5 publications vs ≤4 (1.46 (1.16-1.83); p = 0.001). Odds of matching were lower among PS (0.50 (0.36-0.69); p < 0.001) and TS (0.2 (0.13-0.31); <0.001) compared to GS applicants. Participants had higher odds of matching when having >240 step 1 score vs ≤239 (1.33 (1.04-1.70); p = 0.026), >250 step 2 score vs ≤249 (1.52 (1.20-1.92); p < 0.001), and were more likely to match at a program where they indicated a geographic preference (5.49 (2.58-11.66); p < 0.0001) or program signal (3.87 (1.85-8.11); p < 0.001)., Conclusions: The novel geographic preferencing and program signal functions were associated with increased match success. More studies are needed to assess the generalizability of these findings., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

To delineate the mechanisms by which the ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS-driven cancer growth, we determined the ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer. We determined that ERK1 and ERK2 share near-identical signaling and transforming outputs and that the KRAS-regulated phosphoproteome is driven nearly completely by ERK. We identified 4666 ERK-dependent phosphosites on 2123 proteins, of which 79 and 66%, respectively, were not previously associated with ERK, substantially expanding the depth and breadth of ERK-dependent phosphorylation events and revealing a considerably more complex function for ERK in cancer. We established that ERK controls a highly dynamic and complex phosphoproteome that converges on cyclin-dependent kinase regulation and RAS homolog guanosine triphosphatase function (RHO GTPase). Our findings establish the most comprehensive molecular portrait and mechanisms by which ERK drives KRAS-dependent pancreatic cancer growth.

How the KRAS oncogene drives cancer growth remains poorly understood. Therefore, we established a systemwide portrait of KRAS- and extracellular signal-regulated kinase (ERK)-dependent gene transcription in KRAS-mutant cancer to delineate the molecular mechanisms of growth and of inhibitor resistance. Unexpectedly, our KRAS-dependent gene signature diverges substantially from the frequently cited Hallmark KRAS signaling gene signature, is driven predominantly through the ERK mitogen-activated protein kinase (MAPK) cascade, and accurately reflects KRAS- and ERK-regulated gene transcription in KRAS-mutant cancer patients. Integration with our ERK-regulated phospho- and total proteome highlights ERK deregulation of the anaphase promoting complex/cyclosome (APC/C) and other components of the cell cycle machinery as key processes that drive pancreatic ductal adenocarcinoma (PDAC) growth. Our findings elucidate mechanistically the critical role of ERK in driving KRAS-mutant tumor growth and in resistance to KRAS-ERK MAPK targeted therapies.