© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 13, 1032,
July 3, 2002
© 2002 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Blocking Oncogenic Ras Signaling for Cancer Therapy
Correspondence to: Alex A. Adjei, M.D., Ph.D., Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (e-mail: adjei.alex{at}mayo.edu).
I have read with interest the excellent letter from Canevari, Biocca, and Figini.
The diversion of Ras localization from membrane by intracellular antibodies is indeed a promising and attractive approach to the inhibition of oncogenic ras signaling. The failure to include this approach in my review article was not due to space limitations or a major focus on traditional pharmacologic approaches. It was, rather, due to the decision to focus predominantly on approaches for which phase I human clinical studies had at least commenced.
This explains why other potential approaches with provocative preclinical data such as 1) the ability of trans-farnesylthiosalicylic acid to reduce the amounts of membrane-associated Ras by dislodging Ras protein from its anchorage domains and thus facilitating Ras degradation and reducing the amount of total cellular Ras (1,2), and 2) Ras C-terminal sequence-specific endoprotease inhibitors such as UM96001, TPCK, and BFCCMK that have been shown to inhibit human cancer cells and selectively induce apoptosis (3) were not included in this review. However, I would like to thank the authors for highlighting the intracellular antibody approach that has yielded interesting results with HER-2/neu targeting and clearly holds promise for the interruption of Ras(p21) signaling.
REFERENCES
1 Jansen B, Heere-Ress E, Schlagbauer-Wadl H, Halaschek-Wiener J, Waltering S, Moll I, et al. Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice. J Mol Med 1999;77:792–7.[CrossRef][Web of Science][Medline]
2
Jansen B, Schlagbauer-Wadl H, Kahr H, Heere-Ress E, Mayer BX, Eichler H, et al. Novel Ras antagonist blocks human melanoma growth. Proc Natl Acad Sci U S A 1999;96:14019–24.
3 Chen Y. Inhibition of K-ras-transformed rodent and human cancer cell growth via induction of apoptosis by irreversible inhibitors of Ras endoprotease. Cancer Lett 1998;131:191–200.[CrossRef][Web of Science][Medline]
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