한빛사 논문
Jason K. Sa1,†, Jung Yong Hong2,†, In-Kyoung Lee2, Ju-sun Kim2, Moon-Hee Sim2, Ha Jung Kim2, Ji Yeong An3, Tae Sung Sohn3, Joon Ho Lee3, Jae Moon Bae3, Sung Kim3, Kyoung-Mee Kim4, Seung Tae Kim2, Se Hoon Park2, Joon Oh Park2, Ho Yeong Lim2, Won Ki Kang2, Nam-Gu Her5, Yeri Lee5, Hee Jin Cho5, Yong Jae Shin5, Misuk Kim5, Harim Koo5,6, Mirinae Kim5, Yun Jee Seo5, Ja Yeon Kim5, Min-Gew Choi3,*, Do-Hyun Nam5,6,7,* and Jeeyun Lee2,*
1Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea. 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 3Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 5Institute for Refractory Cancer Research, Samsung Medical Center, Seoul,
Republic of Korea. 6Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea. 7Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
* Correspondence
†Jason K. Sa and Jung Yong Hong contributed equally to this work.
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.
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