Comprehensive pharmacogenomic characterization of gastric cancer

Jason K. Sa, Jung Yong Hong, In Kyoung Lee, Ju Sun Kim, Moon Hee Sim, Ha Jung Kim, Ji Yeong An, Tae Sung Sohn, Joon Ho Lee, Jae Moon Bae, Sung Kim, Kyoung Mee Kim, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Ho Yeong Lim, Won Ki Kang, Nam Gu Her, Yeri Lee, Hee Jin ChoYong Jae Shin, Misuk Kim, Harim Koo, Mirinae Kim, Yun Jee Seo, Ja Yeon Kim, Min Gew Choi, Do Hyun Nam, Jeeyun Lee

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background: Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. Methods: To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. Results: We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. Conclusions: Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

Original languageEnglish
Article number17
JournalGenome Medicine
Volume12
Issue number1
DOIs
Publication statusPublished - 2020 Feb 18

Keywords

  • Gastric cancer
  • Gefitinib
  • Pharmacogenomics
  • PIK3CA-E542K
  • RNF11

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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