Category: Drug Target Strategies

1321-B - Identification of genomic and molecular traits that present therapeutic vulnerability to HGF-targeted therapy in glioblastoma.

Monday, February 5, 2018
5:00 PM - 6:00 PM

Cancer is a complex disease with profound genomic alterations and extensive heterogeneity. Recent studies on a large-scale genomics have shed lights on the impact of core oncogenic pathways that are frequently dysregulated in a wide spectrum of cancer types. Among them, aberrant activation of HGF signaling axis has been associated with promotion of various oncogenic programs during tumor initiation, progression, and treatment resistance, prompting HGF-targeted therapy as an attractive choice in therapeutic approach. However, recent clinical trials involving HGF-targeted therapies have demonstrated disappointing results, necessitating in-depth assessment of new patient stratification that could shift the current clinical course. To address such challenges, we have evaluated therapeutic efficacy of YYB-101, HGF neutralizing antibody, in a series of primary glioblastoma stem cells (GSCs) to determine genetic traits that present targeted vulnerability to HGF-mediated therapy. As a result, We have identified differentially up-regulated genes associated with tumor invasion and malignancy including MET, KDR, and SOX3 through classification of drug reactivity to YYB-101 using invasion and proliferation assays, and confer unfavorable prognosis in patients with glioblastoma. Additionally, we demonstrated HGF-MET signaling axis as a key molecular determinant in GSC invasion. Collectively, our results provide an important framework for evaluation of HGF-targeted therapy in future clinical course. Collectively, our results provide an important framework for evaluation of HGF-targeted therapy in future clinical course.

SUNGHEON KIM

Student
Samsung Medical Center
Seoul, Seoul-t'ukpyolsi, Republic of Korea

Sung-Heon KIM, in Ph.D program
Sungkyunkwan University, SKKU

Cancer Stem Cell Research Center
Department of Neurosurgery
Samsung Biomedical Research Institute, Samsung Medical Center

Samsung Medical Center annex B3 IRCR,
50 Irwon-dong, Gangnam-gu, Seoul, 06351, South Korea

TEL : +82-2-2148-7341(Lab) / Mobile : +82-10-4855-3466

E-mail: apollocoin@gmail.com