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as paclitaxel. Finally, Mao et al. were able to translate novel and potentially ground-breaking investigations into
[85]
this to an in vivo study evidencing that genetic knockout of the role of Notch not only in HCC, but other cancer types. In
[86]
Notch-1 abrogated tumor xenograft growth. Zhao et al. addition, the study of Notch mediation has radiated toward
reported that the knockdown of Notch-1 by RNA interference different fields of medicine with the intent of delineating
suppressed Akt activation, reduced glioma cell growth rate the roles of isoform-specific NICD. Additionally, the role of
and induce cell apoptosis. cellular homeostasis has interpretive results in a myriad of
clinical and basic science indications and perhaps Notch
Notch-1 deletion has also been studied in HCC. Sun and will be at the forefront of these studies. However, the role
colleagues investigated that knockout of Notch-1 inhibited of Notch in carcinogenesis, albeit, counterintuitive, is both
cell proliferation and significantly suppressed tumor exciting and complex. The early results prove modulation
formation of L02/HBx cells in a BALB/c nude mouse model of this pathway could aid in the care of advanced, resistant,
in vivo through activation of apoptotic caspase cascades. In and aggressive cancer types. These Notch-based strategies
addition, they observed that this blockade arrest the cell cycle will continue to be evaluated and will also be combined with
in the G0/G1 phase through the down regulation of cyclin D1, other pathway mitigation to reduce toxicity profiles, as well as
CDK4, E2F1 and the up regulation of p21. Wang et al. the chemoresistance. Combination with approved and current
[88]
[87]
suggested that the inhibition of Notch1 by shRNA significantly strategies will further the understanding and commitment
suppressed the growth of HBx transformed human hepatic to providing alternative and efficacious treatment options
cells through G0/G1 cell cycle arrest and apoptosis. The to patients with HCC.
mechanism, they suggested, may be linked to the promoted
expression of P16 and decreased expression of Bcl-2. [88] ACKNOWLEDGMENTS

Finally, the investigation into microRNAs as a potential This review was supported by the Medical College of Wisconsin Dean’s
strategy is growing in interest. MicroRNAs are small Development Program, the Medical College of Wisconsin Research
regulators of both post-translational and post-transcriptional Affairs Committee, the Medical College of Wisconsin Digestive
markers. They are often at the center of abrogation in many Disease Center Fund, and the Froedtert Hospital Foundation.
cancer types. [89,90] Given their stability, they are potential
candidates for use in combination studies. For instance, REFERENCES
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