Cancer and Metastasis Reviews

, Volume 32, Issue 1, pp 229–268

Tackling hepatitis B virus-associated hepatocellular carcinoma—the future is now

NON-THEMATIC REVIEW

DOI: 10.1007/s10555-012-9412-6

Cite this article as:
Bharadwaj, M., Roy, G., Dutta, K. et al. Cancer Metastasis Rev (2013) 32: 229. doi:10.1007/s10555-012-9412-6

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers in many developing countries including India. Among the various etiological factors being implicated in the cause of HCC, the most important cause, however, is hepatitis B virus (HBV) infection. Among all HBV genes, HBx is the most critical carcinogenic component, the molecular mechanisms of which have not been completely elucidated. Despite its clinical significance, there exists a very elemental understanding of the molecular, cellular, and environmental mechanisms that drive disease pathogenesis in HCC infected with HBV. Furthermore, there are only limited therapeutic options, the clinical benefits of which are insignificant. Therefore, the quest for novel and effective therapeutic regimen against HBV-related HCC is of paramount importance. This review attempts to epitomize the current state of knowledge of this most common and dreaded liver neoplasm, highlighting the putative treatment avenues and therapeutic research strategies that need to be implemented with immediate effect for tackling HBV-related HCC that has plagued the medical and scientific fraternity for decades. Additionally, this review proposes a novel “five-point” management algorithm for HBV-related HCC apart from portraying the unmet needs, principal challenges, and scientific perspectives that are relevant to controlling this accelerating global health crisis.

Keywords

Hepatitis B virusHBxMolecular mechanismsHepatocellular carcinomaMetastasisTherapeutics

Abbreviations

PCNA-LI

Proliferating cell nuclear antigen labeling index

MIB-1

Mindbomb homolog 1

CAS

Chromosome segregation gene homolog

nm-23

Non-metastatic protein-23

MAD2

Mitotic arrest defective protein 2

CSI

Chromosomal instability

LOH

Loss of heterozygosity

MSI

Microsatellite instability

CDKIs

Cyclin-dependent kinase inhibitors

TOP2A

Topoisomerase II alpha

TERT

Telomerase reverse transcriptase

DLC2

Deleted in liver cancer 2

MMP

Matrix metalloproteases

uPA

Urokinase plasminogen activator

MVD

Microvessel density

VEGF

Vascular endothelial growth factor

VEGFR

Vascular endothelial growth factor receptor

PDEGF

Platelet-derived endothelial growth factor

PCNA

Proliferating cell nuclear antigen

PDEGFR

Platelet-derived endothelial growth factor receptor

FGFR

Fibroblast growth factor receptor

HIF-1α

Hypoxia-inducible factor-1 alpha

NOS

Nitric oxide synthase

b-FGF

Basic fibroblast growth factor

IL-8

Interleukin-8

TNF-α

Tumor necrosis factor-α

TGF-β

Transforming growth factor beta

EGFR

Epidermal growth factor receptor

TSGF

Tumor-specific growth factor

AFP mRNA

Alpha-fetoprotein mRNA

GGT mRNA

Gamma-glutamyl transferase mRNA

IGF-1R

Insulin-like growth factor receptor 1

IGF-II

Insulin-like growth factor-II

CRP

C-reactive protein

miRNA

MicroRNA

BRAF

v-raf Murine sarcoma viral oncogene homolog B1

mTOR

Mammalian target of rapamycin

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Mausumi Bharadwaj
    • 1
  • Gaurav Roy
    • 1
    • 2
  • Koushik Dutta
    • 3
  • Mohammad Misbah
    • 2
  • Mohammad Husain
    • 2
  • Showket Hussain
    • 1
  1. 1.Division of Molecular Genetics & BiochemistryInstitute of Cytology & Preventive Oncology (ICMR)NoidaIndia
  2. 2.Department of BiotechnologyJamia Millia IslamiaNew DelhiIndia
  3. 3.Department of NeurologyMedical College HospitalKolkataIndia