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Extracellular signal-regulated kinase-1/2 (ERK1/2) pathway inhibitors are important therapies for treating many cancers. However, acquired resistance to most protein kinase inhibitors limits their ability to provide durable responses. Approximately 50% of malignant melanomas contain activating mutations in BRAF, which promotes cancer cell survival through the direct phosphorylation of the mitogen-activated protein kinase MAPK/ERK 1/2 (MEK1/2) and the activation of ERK1/2. Although the combination treatment with BRAF and MEK1/2 inhibitors is a recommended approach to treat melanoma, the development of drug resistance remains a barrier to achieving long-term patient benefits. Few studies have compared the global proteomic changes in BRAF/MEK1/2 inhibitor-resistant melanoma cells under different growth conditions. The current study uses high-resolution label-free mass spectrometry to compare relative protein changes in BRAF/MEK1/2 inhibitor-resistant A375 melanoma cells grown as monolayers or spheroids. While approximately 66% of proteins identified were common in the monolayer and spheroid cultures, only 6.2 or 3.6% of proteins that significantly increased or decreased, respectively, were common between the drug-resistant monolayer and spheroid cells. Drug-resistant monolayers showed upregulation of ERK-independent signaling pathways, whereas drug-resistant spheroids showed primarily elevated catabolic metabolism to support oxidative phosphorylation. These studies highlight the similarities and differences between monolayer and spheroid cell models in identifying actionable targets to overcome drug resistance.

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Introduction The COVID-19 pandemic has left more than 38% of households food insecure in the United States. Improved education of food security topics in medical school can improve screening for food insecurity and improve health outcomes. The first aim of this study was to address if participation in an experiential integrative service learning program improved medical students’ understanding of food insecurity. The second aim was to compare knowledge of food insecurity between the general body of medical students and those who participated in the service learning program. Methods This was a cohort study at a large medical school in southeast Michigan in 2019–2020. We administered the Food Insecurity for Health Professionals (FISHP) survey to medical student participants; higher scores on the FISHP survey suggest higher knowledge and comfort with food security topics. We administered online Qualtrics surveys to the volunteer group before and after volunteering 12 hours at an urban farm. We also administered a one-time survey to a control group of medical students. We performed univariable and bivariable statistical analyses with StataSE 16. The study was exempted by the institutional IRB. Results Medical students in the volunteer group (n = 18) and the control group (n = 66) completed online surveys. Participants in the volunteer group had increased knowledge of food security after volunteering in the service learning program (p = .03). There was a statistically significant difference between the mean FISHP scores for the control group and the volunteer group (p = .001). Conclusion Medical student participation in an experiential integrative service learning program improved knowledge of food security topics and increased comfort discussing food insecurity with patients, compared to students who did not participate. Experiential integrative service learning may improve holistic patient care through physician recognition of food insecurity and other social determinants of health.