Antitumoral activity of synthetic peptides Crotalicidin and NA-CATH-ATRA-1-ATRA-1 as an alternative approach for therapy in breast cancer and ovarian cancer
Antitumoral activity of synthetic peptides Crotalicidin and NA-CATH-ATRA-1-ATRA-1 as an alternative approach for therapy in breast cancer and ovarian cancer
Cancer remains a leading global health challenge, especially aggressive subtypes like triple-negative breast cancer (TNBC) and ovarian clear cell carcinoma (OCCC), which often develop resistance to standard therapies. This doctoral thesis of Vanessa Gallego Londoño explores a promising alternative: synthetic bioactive peptides (small proteins) based on snake venom that disrupt cancer cell membranes. Because this mechanism depends on physical interactions and does not rely on specific receptors, it can bypass standard drug resistance mechanisms.
We investigated two synthetic peptides: Crotalicidin (Ctn), derived from the South American rattlesnake, and NA-CATH-ATRA-1-ATRA-1 (NA), based on the Chinese cobra. Both peptides demonstrated potent tumor cell-killing activity in laboratory models of breast and ovarian cancer. NA showed exceptional potency, even surpassing a positive control anticancer peptide currently in clinical trials (LTX-315), which is administered via local injection into tumors.
Importantly, our research showed that Ctn and NA do not just kill cancer cells directly. In TNBC models, the rapid membrane destruction caused by the peptides triggers "immunogenic cell death," releasing danger signals that recruit and activate Natural Killer (NK) immune cells. Activation of the immune system can help clear the tumor and distant metastases. Furthermore, in OCCC models, pre-treating cancer cells with cholesterol-lowering drugs such as simvastatin significantly sensitized the cells, making them more vulnerable to peptide-induced membrane disruption.
In summary, this thesis demonstrates that snake venom-based synthetic peptides represent a promising therapeutic strategy that can directly eradicate aggressive cancer cells, activate the patient's immune system, and synergize with existing clinical drugs.