**7. Discussion**

BC ranks first in terms of frequency and mortality in the world [2]. Metastasis is responsible for 90% of deaths [53] and some integrins such as αvβ3, α5β1 and αvβ6 are involved in this process [31, 47, 54]. It has been observed that disintegrins may be an approach for future treatments by inhibiting the activity of integrins in cancer [11, 18, 55]. **Table 1** lists the disintegrins with effects on BC (cell line MCF-7) and TNBC (cell line MDA-MB-231). Most of them cause alterations in cell migration and adhesion.

We also find recombinant disintegrins such as Dis*Ba-01* [44], r-viridistatin [46], and vicrostatin with promising pharmacological activity on cancer progression [51, 52]. Vicrostatin, is a chimeric recombinant disintegrin, produced as a genetic fusion between the C-terminal tail of echistatin and contortrostatin, it has shown the greatest anti-cancer potential [51] and several studies have evaluated its effect. Vicrostatin encapsulated in liposomes, was tested *in vivo* showing >80% of decrease in tumor growth and increased survival, similar results to those obtained in the group treated with the monoclonal antibody bevacizumab, used as the gold standard in antiangiogenic therapy [52]. Vicrostatin has also shown promising results in ovarian cancer [56], prostate cancer [57] as well as a diagnostic marker in glioma [58].

Contortrostatin is noteworthy for being the first work using human cell primary culture extracted from BC tissue. These primary cells maintain the original cellular phenotype, which is desirable for cell binding and motility experiments, effects present in metastasis [43].

In this review we only considered papers about human BC, we decided to discard the effect of crotoxin 2 because its effect was evaluated in murine breast cancer lines (66.3p). The effects of crotoxin 2 were the same as those disintegrins which cause inhibition of cell migration. In contrast to other disintegrins, to achieve a decrease in lung colonization crotoxin 2 required 1000 μg/kg, high doses to avoid the metastatic effect [59]. It would now need to be tested in human cancer lines to demonstrate if it has the same effects.

Other papers not considered were those naming cell lines as belonging to breast cancer [60–64], but recently, several studies have confirmed that they are melanoma lines [65–67]. We also do not to include the study of the disintegrin Disba-01 evaluated on the MDA-MB-231 (TNBC cell line) because it had no effect on the binding nor cell proliferation [68].

It has been demonstrated that disintegrins have high selectivity in the binding and inhibition of integrins, an activity highlighted for their therapeutic potential [31]; thus, this review shows the panorama and potential of disintegrins in BC, but there are still more studies and problems to be solved in order to reach their clinical application.
