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Cancer Treat Rev. 2016 Apr;45:77-86. doi: 10.1016/j.ctrv.2016.02.008. Epub 2016 Mar 2.

Personalized therapy for hepatocellular carcinoma: Where are we now?

Author information

1
State Key Laboratory of Oncology in South China, The Chinese University of Hong Kong, Hong Kong; Sir YK Pao Center for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute, and Prince of Wales Hospital, Hong Kong; Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong. Electronic address: chanlam_stephen@cuhk.edu.hk.
2
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong. Electronic address: Alissa_48@yahoo.com.
3
Sir YK Pao Center for Cancer, Department of Clinical Oncology, Hong Kong Cancer Institute, and Prince of Wales Hospital, Hong Kong. Electronic address: kirsty.lee@gmail.com.
4
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong. Electronic address: natwong@cuhk.edu.hk.
5
State Key Laboratory of Oncology in South China, The Chinese University of Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong. Electronic address: allen@cuhk.edu.hk.

Abstract

Following the approval of sorafenib, a large number of molecular targeted agents have been tested clinically for advanced hepatocellular carcinoma (HCC), but all have failed to demonstrate significant efficacy in clinical trials. Multiple reasons for this phenomenon have been discussed in the literature, with one reason being the lack of patient selection on the basis of molecular profile in clinical trials. The concept of drug testing in selected populations has been recently suggested by retrospective analyses of HCC clinical trials in which a particular subgroup of patients, either enriched by clinical factors or by tissue biomarkers, derived more benefits from the novel drug. In addition, recent advances in genomic medicine have enhanced the understanding of genetic and epigenetic events occurring in HCC, raising the possibility of personalizing targeted agents in accordance with the genetic make-up of the tumors. The development of 'personalized' treatment for HCC is, however, hindered by the lack of fresh biopsy of advanced HCC, the low incidence of genetic driver mutations in HCC and the tumor heterogeneity. These limitations may be overcome by sequencing cell-free DNA in plasma, frequently known as liquid biopsy, and revolution in the concept of the design of clinical trials. In this review article, we aim to: (1) give a summary of the recent sequencing results of HCC and the related implications for drug development; (2) highlight potential individual targeted agents and existing research on biomarker selection in clinical trials; and (3) discuss future directions, including the potential of liquid biopsy and umbrella clinical trials, to enhance personalized drug testing for HCC.

KEYWORDS:

Biomarker; Drug; Liver neoplasm; Targeted therapy

PMID:
26995632
DOI:
10.1016/j.ctrv.2016.02.008
[Indexed for MEDLINE]

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