Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world; there is an increasing incidence worldwide, and approximately 500,000 new cases are reported per year. More than 75% of cases occur in the Asia-Pacific region, largely in association with chronic hepatitis B virus (HBV) infection. In most cases, HCC is diagnosed at a late stage. Therefore, the prognosis of patients with HCC is generally poor and has a less than 5% 5-year survival rate. The recommended screening strategy for patients with cirrhosis includes the determination of serum alpha-fetoprotein (AFP) levels and an abdominal ultrasound every 6 months to detect HCC at an earlier stage, when it is amenable to effective treatment strategies. AFP, however, is a marker characterized by poor sensitivity and specificity, and abdominal ultrasound is an imaging technology that is highly dependent on the operator’s experience.In addition to AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3), des-carboxy prothrombin (DCP), glypican-3 (GPC-3), osteopontin (OPN), and several other biomarkers (such as squamous cell carcinoma antigen immunoglobulin M complexes, alpha-1- fucosidase [AFU], chromogranin A [CgA], human hepatocyte growth factor, and insulin-like growth factor [IGF]) have been proposed as markers for the early detection of HCC. None of them is optimal; however, when used together, their sensitivity in detecting HCC is increased. Recent developments in gene-expressing microarrays and proteomics promise even more potential diagnostic options.More recent research has demonstrated that some of these tumor markers (such as DCP, GPC-3, OPN), in addition to diagnostic and prognostic role in HCC, stimulate HUVEC growth and migration; growth of HCC cells by upregulating autocrine/paracrine canonical Wnt signaling; and Met-Janus kinase 1-signal transducer and activator of transcription 3 (Met-JAK1-STAT3) signaling pathway, which results in HCC cell proliferation. Therefore, these tumor markers have an important role in hepatocarcinogenesis and this could have an important opportunity in the HCC treatment.In the near future, research will have to deal with molecular targeted therapy with a focus on angiogenesis, growth signals, and mitotic abnormalities, as well as the promising concepts of “cancer stemness” and “synthetic lethality” for the strategy of targeted therapy.In conclusion, effective molecularly targeted therapies may also hold promise as adjuvants to primary surgical therapies, currently limited by high rates of disease recurrence. It is hoped that, active research aimed at the elucidation of the molecular pathogenesis of HCC and the identification of new biomarkers will result in further advances in the prevention, diagnosis, and treatment of HCC. Finally, in multi-disciplinary standardized treatment will be needed with Individualized plan for different patients or a single patient at different stages.

Hepatocellular Carcinoma: present and future

BERTINO, Gaetano
2012

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world; there is an increasing incidence worldwide, and approximately 500,000 new cases are reported per year. More than 75% of cases occur in the Asia-Pacific region, largely in association with chronic hepatitis B virus (HBV) infection. In most cases, HCC is diagnosed at a late stage. Therefore, the prognosis of patients with HCC is generally poor and has a less than 5% 5-year survival rate. The recommended screening strategy for patients with cirrhosis includes the determination of serum alpha-fetoprotein (AFP) levels and an abdominal ultrasound every 6 months to detect HCC at an earlier stage, when it is amenable to effective treatment strategies. AFP, however, is a marker characterized by poor sensitivity and specificity, and abdominal ultrasound is an imaging technology that is highly dependent on the operator’s experience.In addition to AFP, Lens culinaris agglutinin-reactive AFP (AFP-L3), des-carboxy prothrombin (DCP), glypican-3 (GPC-3), osteopontin (OPN), and several other biomarkers (such as squamous cell carcinoma antigen immunoglobulin M complexes, alpha-1- fucosidase [AFU], chromogranin A [CgA], human hepatocyte growth factor, and insulin-like growth factor [IGF]) have been proposed as markers for the early detection of HCC. None of them is optimal; however, when used together, their sensitivity in detecting HCC is increased. Recent developments in gene-expressing microarrays and proteomics promise even more potential diagnostic options.More recent research has demonstrated that some of these tumor markers (such as DCP, GPC-3, OPN), in addition to diagnostic and prognostic role in HCC, stimulate HUVEC growth and migration; growth of HCC cells by upregulating autocrine/paracrine canonical Wnt signaling; and Met-Janus kinase 1-signal transducer and activator of transcription 3 (Met-JAK1-STAT3) signaling pathway, which results in HCC cell proliferation. Therefore, these tumor markers have an important role in hepatocarcinogenesis and this could have an important opportunity in the HCC treatment.In the near future, research will have to deal with molecular targeted therapy with a focus on angiogenesis, growth signals, and mitotic abnormalities, as well as the promising concepts of “cancer stemness” and “synthetic lethality” for the strategy of targeted therapy.In conclusion, effective molecularly targeted therapies may also hold promise as adjuvants to primary surgical therapies, currently limited by high rates of disease recurrence. It is hoped that, active research aimed at the elucidation of the molecular pathogenesis of HCC and the identification of new biomarkers will result in further advances in the prevention, diagnosis, and treatment of HCC. Finally, in multi-disciplinary standardized treatment will be needed with Individualized plan for different patients or a single patient at different stages.
Hepatocellular Carcinoma; HCC biomarkers; HCC diagnosis; HCC treatment
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/32830
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact