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

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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.

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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

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Acknowledgments

The authors are thankful to the Indian Council of Medical Research (ICMR), New Delhi, and the Institute of Cytology and Preventive Oncology (ICPO-ICMR) for funding and fellowship support to Gaurav Roy.

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The authors declare that they have no conflict of interest.

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Correspondence to Mausumi Bharadwaj or Showket Hussain.

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Bharadwaj, M., Roy, G., Dutta, K. et al. Tackling hepatitis B virus-associated hepatocellular carcinoma—the future is now. Cancer Metastasis Rev 32, 229–268 (2013). https://doi.org/10.1007/s10555-012-9412-6

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