Textbook of Personalized Medicine - Second Edition [2015]

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outcomes and the potential for cancer recurrence in patients with HCC and to iden-
tify differing subgroups of patients where surgery and targeted therapies are more
effective. Pfi zer is evaluating IntegraGen’s 56-gene molecular signature of HCC for
classifi cation into six categories to predict prognosis.
Interferon (IFN) has a signifi cant benefi cial effect after curative treatment of HCC
in terms of both survival and tumor recurrence. A multikinase inhibitor sorafenib has
also been reported to enhance survival. Despite several treatment options, fewer than
half of candidates for potentially curative treatments receive them.
Targeted adjuvant therapies require methods to guide selection of optimal treat-
ment for HCC. HCC can be classifi ed in molecular classes according to Wnt-beta-
catenin pathway activation, proliferation signature activation (associated with
chromosomal instability), and other subgroups. A molecular classifi cation is essen-
tial to enable the development of new targets, and to customize therapies in patients
with HCC (Villanueva et al. 2008 ).
The expression patterns of miRNAs in liver tissue differ between men and
women with hepatocellular carcinoma. The miR-26 expression status of such
patients is associated with survival and response to adjuvant therapy with IFN-α. A
study showed that patients whose tumors had low miR-26 expression had shorter
overall survival but a better response to IFN-α than patients whose tumors had high
expression of the miRNA (Ji et al. 2009 ). This has implications for the personalized
management of liver cancer.


Prediction of Recurrence of Hepatocellular Carcinoma


Typically observed at 2 years after surgical resection, late recurrence is a major
challenge in the management of HCC. Systematic analysis of gene expression data
from human liver undergoing hepatic injury and regeneration revealed 233-gene
signature that was signifi cantly associated with late recurrence of HCC (Kim et al.
2014b ). Using this signature, the authors developed a prognostic predictor that can
identify patients at high risk of late recurrence validated the robustness of the pre-
dictor in patients. The potential signifi cance of STAT3 activation in late recurrence
was predicted by gene network analysis and validated later. Two independently
developed predictors refl ected well the differences between early and late recur-
rence of HCC at the molecular level and provided new biomarkers for risk stratifi ca-
tion. The main limitation of the study is that most of the patients were hepatitis B
virus-positive. Further investigations are needed to test these prediction models in
patients with different causes of HCC, such as hepatitis C virus.


Personalized Management of Lung Cancer


Globally, >1.6 million new cases of lung malignancies are diagnosed annually with
about 85 % having NSCLC, who often have advanced disease and a low survival
rate. It is important to have targeted therapies as well as companion diagnostics to
guide the selection of patients most likely to respond to these treatments.


10 Personalized Therapy of Cancer
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