PMID- 27751352
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 9
IP  - 5
DP  - 2016 Oct
TI  - Loss of Tuberous Sclerosis Complex 2 (TSC2) as a Predictive Biomarker of Response 
      to mTOR Inhibitor Treatment in Patients with Hepatocellular Carcinoma.
PG  - 466-471
LID - S1936-5233(16)30087-0 [pii]
LID - 10.1016/j.tranon.2016.08.009 [doi]
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related 
      death globally. Mechanistic target of rapamycin (mTOR) is frequently up-regulated 
      in HCC and plays an important role in HCC tumorigenesis. Tumors with loss of 
      tuberous sclerosis complex 2 (TSC2), a negative regulator of mTOR signaling, tend 
      to respond well to mTOR inhibitors. We analyzed TSC2 expression status in Korean 
      patients with HCC and evaluated the correlation between TSC2 loss and response to 
      the mTOR inhibitor, everolimus. METHODS: We retrospectively assessed 36 patients 
      with advanced HCC who had received sorafenib at a single center in Korea between 
      2008 and 2014, and for whom tumor specimens were available for TSC2 
      immunohistochemical analysis (IHC). Three patient-derived tumor cell lines (PDCs) 
      were analyzed by western blotting to determine TSC2 expression and drug 
      sensitivity to mTOR. RESULTS: Twelve of 36 patients (33.3%) showed low to 
      undetectable levels of TSC2 expression. No significant differences were observed 
      in progression-free survival (PFS) or overall survival with sorafenib treatment 
      based on TSC2 expression status. Two patients were treated with everolimus after 
      sorafenib failure; one patient, with moderate TSC2 expression, experienced stable 
      disease with a PFS of 5.8 months; the other, with high TSC2 expression, 
      experienced rapid progression. PDC models demonstrated that the TSC2-low HCC PDC 
      line was significantly more sensitive to everolimus than the TSC2-high HCC PDC 
      lines. CONCLUSION: Loss of TSC2 may predict improved response to everolimus in 
      HCC patients, but further studies are needed to confirm the predictive role of 
      TSC2 expression for everolimus treatment.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Cho, Jinhyun
AU  - Cho J
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Lee, Jeeyun
AU  - Lee J
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Kim, Jusun
AU  - Kim J
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Kim, Seung Tae
AU  - Kim ST
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Lee, Sujin
AU  - Lee S
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Kim, Sun Young
AU  - Kim SY
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
FAU - Ha, Sang Yun
AU  - Ha SY
AD  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine, Seoul, Republic of Korea.
FAU - Park, Cheol-Keun
AU  - Park CK
AD  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine, Seoul, Republic of Korea. Electronic address: ckpark@skku.edu.
FAU - Lim, Ho Yeong
AU  - Lim HY
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center 
      Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic 
      address: hoylim@skku.edu.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC5067924
EDAT- 2016/10/19 06:00
MHDA- 2016/10/19 06:01
PMCR- 2016/10/14
CRDT- 2016/10/19 06:00
PHST- 2016/06/14 00:00 [received]
PHST- 2016/08/22 00:00 [revised]
PHST- 2016/08/24 00:00 [accepted]
PHST- 2016/10/19 06:00 [pubmed]
PHST- 2016/10/19 06:01 [medline]
PHST- 2016/10/19 06:00 [entrez]
PHST- 2016/10/14 00:00 [pmc-release]
AID - S1936-5233(16)30087-0 [pii]
AID - 10.1016/j.tranon.2016.08.009 [doi]
PST - ppublish
SO  - Transl Oncol. 2016 Oct;9(5):466-471. doi: 10.1016/j.tranon.2016.08.009.