Moving towards personalised therapy in patients with hepatocellular carcinoma: the role of the microenvironment

被引:89
作者
Giannelli, Gianluigi [1 ]
Rani, Bhavna [1 ]
Dituri, Francesco [1 ]
Cao, Yuan [1 ]
Palasciano, Giuseppe [1 ]
机构
[1] Univ Bari, Sch Med, Dept Biomed Sci & Human Oncol, Bari, Italy
关键词
ENDOTHELIAL GROWTH-FACTOR; E-CADHERIN EXPRESSION; GENE-EXPRESSION; CELL-MIGRATION; FACTOR CTGF; PHASE-II; MATRIX METALLOPROTEINASE-2; TUMOR XENOGRAFTS; LAMININ-5; SORAFENIB;
D O I
10.1136/gutjnl-2014-307323
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The goal of personalised therapy based on hepatocellular carcinoma (HCC) molecular characteristics is still beyond our grasp. Systemic treatments show poor efficacy, mainly because of the great heterogeneity of the tumour. Indeed, differences in aetiology, disease stage and biochemical composition of the fibrotic liver make cirrhosis itself a highly dyshomogeneous disease. Cancer cells grow in a cirrhotic microenvironment, interacting with stromal cells and engaging matrix components that differ from patient to patient, hampering the development of drugs to treat all patients. Growing evidence suggests a role for the crosstalk between HCC and the host stroma in driving disease progression and hence prognosis and survival. Many efforts have been devoted to identifying genes responsible for good or bad prognosis, but no study has yet proven helpful in guiding therapeutic choices and management over time, also taking into account the development of drug resistance. The questions of what to target and in which patient are still unsolved. In the personalised therapy scenario, the patient rather than the disease becomes the target of the therapy. However, this still requires an evidence-based medical approach. Herein, we will discuss how individual differences in terms of quality and quantity of the tissue microenvironment components affect progression of HCC. Then, we will highlight potential druggable pathways, also considering ongoing clinical trials. The development of biomarkers will be discussed in the light of new experimental research conducted with the aim of moving towards personalised therapy in patients with HCC.
引用
收藏
页码:1668 / 1676
页数:9
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