AFPep

AFPep is a cyclic nonapeptide with molecular weight 969 D and is derived from the antioncogenic active site of alpha fetoprotein (AFP). Using the standard amino acid abbreviations, AFPep has the sequence cyclo(EKTOVNOGN), where O is hydroxyproline. This peptide has been shown to be useful for the treatment or prevention of ER+ breast cancer in animal models.

Biological activity

"Anti cancer effects:" AFPep inhibits the proliferation of estrogen receptor-positive human breast cancer cells growing in culture (1). It is able to inhibit the estrogen stimulated growth of human breast cancer cells growing as xenografts in immune deficient mice (1). According to a recent study, AFPep prevents the development of carcinogen-induced breast cancer in an animal model (2). AFPep may act as a novel therapeutic or preventive agent for treating estrogen receptor-positive breast cancer.

"Anti estrogenic effects:" AFPep inhibits estrogen-stimulated growth of immature mouse uterus and thus is antiestrogenic (3). In culture, AFPep inhibits the estrogen induced proliferation of T47D cells but has no effect on the basal growth (4). AFPep also inhibits phosphorylation of the estrogen receptor and activates the phosphorylation of p53 (4).

Comparison to Tamoxifen

"AFPep increases the efficacy and decreases the toxicities of Tamoxifen"
Tamoxifen has been a very effective drug for the treatment of estrogen receptor-positive breast cancer. But tamoxifen has certain toxicities and side effects (6,7,8) such as uterine hyperplasia which can lead to endometrial cancer. Moreover some breast cancers acquire resistance to tamoxifen during the course of treatment and few are totally resistant to it. It has been established that AFPep when used in combination with tamoxifen, reduces the uterine hyperplasia and increases the antitumour effects of tamoxifen (5). A rational combination of AFPep and tamoxifen may prove to be a better chemopreventive or chemotherapeutic approach against estrogen receptor-positive breast cancer (5).

Route of administration

AFPep remains actively effective whether it is administrated by intraperitoneal, subcutaneous or oral routes (4).

Future prospects

AFPep could be developed for the prevention and treatment of breast cancer in humans.

References

1. L. A. DeFreest "et al." (2004). “Synthetic peptide derived from alpha-fetoprotein inhibits growth of human breast cancer: investigation of the pharmacophore and synthesis optimization.” J. Peptide Res. 63 (2004): 409-19.

2. Rahul R. Parikh "et al." (2005). “Prevention of N- Methyl N- Nitrosourea – induced Breast Cancer by alpha fetoprotein (AFP) – derived peptide, a peptide derived from the active site of AFP”. Clin Cancer Res. 11 (23): 8512-20.

3. Fassil B. Mesfin "et al." (2000).” Alpha-fetoprotein-derived antiestrotrophic octapeptide”. Biochemica et Biophysica Acta. 1501(2000): 33-43.

4. James A Bennett "et al." (2006). “AFPep: an anti- breast cancer peptide that is orally active”. Breast Cancer Res. and Treatment. 98 (2): 133-41.

5. Thomas T. Andersen "et al." (2007). “An alpha-fetoprotein- derived peptide reduces the uterine hyperplasia and increases the antitumour effect of tamoxifen”. British Journal of Cancer. 97 (3): 327-33.

6. Fisher, B., et al., Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst, 1998. 90(18): p. 1371-88.

7. Assikis, V.J. and V.C. Jordan, Gynecologic effects of tamoxifen and the association with endometrial carcinoma. Int J Gynaecol Obstet, 1995. 49(3): p. 241-57.

8. Kraft, J.K. and T. Hughes, Polypoid endometriosis and other benign gynaecological complications associated with Tamoxifen therapy-a case to illustrate features on magnetic resonance imaging. Clin Radiol, 2006. 61(2): p. 198-201.