The advancement of modern
therapy concepts has dramatically extended the postsurvival rates of patients with malignant
gastric cancer. However, a remaining setback is the drug resistance of recurrent
cancer, which casts a dark shadow over disease prognosis. The original work of Klein et al. [Proteomics Clin. Appl. 2013, 7, 813-824] has outlined a rational experimental approach to decipher the mechanistic pathway of
cancer drug resistance by proteomic approach. They used gel-based comparative proteomics to analyze the nuclear
proteome of a human
gastric cancer cell line (AGS) with and without inactivation of
hypoxia-inducible factor 1 (HIF-1), a
transcription factor and master regulator of
hypoxia adaptation. Using the classical 2DE-MS approach, these researchers observed 163 HIF-1 responsive
proteins, among which over half of them could be confidently identified by MS. From this large dataset, the authors proposed an enhanced nuclear translocation of some proteasomal
proteins upon inactivation of HIF-1. Overall, this work appropriately used proteomics as a hypothesis-free, top-down approach to dissect imperative clinical problems.