The Novel Gamma Secretase Inhibitor RO4929097 Reduces the Tumor Initiating Potential of Melanoma Inhibition of NOTCH Pathway in Melanoma
2011

Gamma Secretase Inhibitor RO4929097 Reduces Melanoma Tumor Initiation

Sample size: 20 publication Evidence: moderate

Author Information

Author(s): Huynh Chanh, Poliseno Laura, Segura Miguel F., Medicherla Ratna, Haimovic Adele, Menendez Silvia, Shang Shulian, Pavlick Anna, Shao Yongzhao, Darvishian Farbod, Boylan John F., Osman Iman, Hernando Eva

Primary Institution: New York University School of Medicine

Hypothesis

Is targeting the NOTCH signaling pathway a valid therapeutic approach against melanoma?

Conclusion

The study found that RO4929097 effectively reduces the tumor initiating potential of melanoma cells.

Supporting Evidence

  • RO4929097 decreased the levels of NOTCH target HES1 in melanoma cell lines.
  • Treatment with RO4929097 reduced cell proliferation and colony formation in soft agar.
  • RO4929097 impaired the formation of melanospheres in melanoma cells.
  • RO4929097 treatment led to smaller secondary tumors in xenotransplantation assays.
  • High levels of NOTCH signaling components were associated with shorter post-recurrence survival in melanoma patients.

Takeaway

A new drug called RO4929097 can help stop melanoma cells from growing and forming new tumors.

Methodology

The effects of RO4929097 were tested on melanoma cell lines in vitro and in vivo using xenograft models.

Limitations

The study did not sort melanoma cells for specific markers, which may affect the interpretation of results.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0025264

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