Reference Detail

Ref Type

Journal Article

PMID

(32070411)

Authors

Sa JK, Hong JY, Lee IK, Kim JS, Sim MH, Kim HJ, An JY, Sohn TS, Lee JH, Bae JM, Kim S, Kim KM, Kim ST, Park SH, Park JO, Lim HY, Kang WK, Her NG, Lee Y, Cho HJ, Shin YJ, Kim M, Koo H, Kim M, Seo YJ, Kim JY, Choi MG, Nam DH, Lee J

Title

Comprehensive pharmacogenomic characterization of gastric cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Genome medicine	12	1	2020 Feb 18	17	Genome Med

URL

Abstract Text

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.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.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.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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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
PIK3CA E542K	stomach cancer	sensitive	Capivasertib	Case Reports/Case Series	Actionable	In a clinical case study, treatment with Truqap (capivasertib) in a patient with gastric cancer harboring PIK3CA E542K resulted in a partial response, and in preclinical studies, led to decreased cell proliferation in a gastric cancer cell line harboring PIK3CA E542K (PMID: 32070411).	32070411
PIK3CA E545K	stomach cancer	sensitive	Capivasertib	Preclinical - Cell culture	Actionable	In a preclinical study, a gastric cancer cell line harboring PIK3CA E545K was sensitive to treatment with Truqap (capivasertib), demonstrating decreased cell proliferation in culture (PMID: 32070411).	32070411