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.