Journal: Cancer Research Communications

Article Title: Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors

doi: 10.1158/2767-9764.CRC-25-0489

Figure Lengend Snippet: Combination treatment with EGFR and KRAS G12C inhibitors overcomes sotorasib resistance due to PTPRR downregulation. A, Cell viability assay for H2122 cells transfected with nonspecific control (siSCR) or PTPRR-specific (siPTPRR) siRNAs and then exposed to the indicated concentrations of sotorasib for 72 hours. B, Immunoblot analysis of PTPRR as well as total and phosphorylated forms of AKT and ERK in H2122 cells transfected with siRNAs as in ( A ) and then incubated with or without sotorasib (1 μmol/L) for 4 hours. C, Cell viability assay for H2122AR30 cells stably transfected with control (GFP) or PTPRR expression plasmids and treated with the indicated concentrations of sotorasib for 72 hours. D, Immunoblot analysis of total or phosphorylated forms of EGFR, AKT, and ERK in H2122AR30 cells treated with sotorasib (1 μmol/L), cetuximab (10 μg/mL), or the combination of both drugs for 4 hours. E, Colony formation assay for H2122 and H2122AR30 cells incubated with or without sotorasib (1 μmol/L), cetuximab (10 μg/mL), or both drugs for 4 weeks. Surviving cells were stained with crystal violet. Data in A and C are means ± SD ( n = 3 independent experiments), and those in B , D , and E are representative of at least three independent experiments.

Article Snippet: Sotorasib, adagrasib and osimertinib were obtained from MedChemExpress, and cetuximab was from Bristol Myers Squibb.

Techniques: Viability Assay, Transfection, Control, Western Blot, Incubation, Stable Transfection, Expressing, Colony Assay, Staining

Journal: Cancer Research Communications

Article Title: Constitutive EGFR Activation Induced by PTPRR Downregulation Confers Resistance to KRAS Inhibitors

doi: 10.1158/2767-9764.CRC-25-0489

Figure Lengend Snippet: EGFR inhibition overcomes resistance to sotorasib in CDX tumors. Experiments were performed using H2122 ( A ) and PTPRR-downregulated H2122AR30 cells ( B ). A, Nude mice harboring H2122 xenografts were treated orally with sotorasib (100 mg/kg, daily) or vehicle (control). The time course of mean tumor volume (left) and relative tumor growth for individual tumors ( n = 8) after treatment for 28 days (right) is shown. B, Nude mice harboring H2122AR30 xenografts were treated orally with sotorasib (100 mg/kg, daily) and i.p. with cetuximab (40 mg/kg, twice weekly) as indicated. The time course of mean tumor volume (left) and relative tumor growth for individual tumors ( n = 8) after treatment for 28 days (right) is shown. C and D, Time course of mean body weight for tumor-bearing mice as in A and B , respectively. All time course data are means ± SEM. The P values for the indicated comparisons in A and B were determined using the unpaired t test.

Article Snippet: Sotorasib, adagrasib and osimertinib were obtained from MedChemExpress, and cetuximab was from Bristol Myers Squibb.

Techniques: Inhibition, Control