NEOADJUVANT TREATMENT OF BREAST CANCER WITH THE PEPTIDE LW-9 AND EVALUATION OF DISEASE-FREE SURVIVAL IN A MURINE MODEL

• Grant number: 25/00012-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: June 30, 2026
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Catarina Raposo Dias Carneiro
• Grantee: Sabrina Carvalho Brunelli
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Breast cancer is the second most common neoplasm in women (second only to non-melanoma skin tumors). The treatment of this disease presents several clinical challenges, such as its high mortality rate and the use of medications that have several adverse effects. Given the need for more specific and less toxic therapies, the use of natural substances, such as animal venoms, appears to be a promising alternative. Our research group demonstrated that the venom obtained from the Phoneutria nigriventer spider contains peptides capable of interfering with the viability, migration, cell cycle and proliferation of cancer cells. The isolated peptide LW-9 was able to reduce tumor mass in a murine model, in addition to increasing efficacy and reducing adverse effects when used in combination with doxorubicin (a classic chemotherapy already used in clinical routine). Furthermore, in the protocol used, the peptide did not present hepatic or renal toxicity. The peptide's mechanism of action is through immunomodulation, increasing signaling between tumor cells and immune system cells. However, initial studies did not evaluate the protocol for use in combination with the main treatment, which is surgery. Neoadjuvant treatment (administration of therapeutic agents before the main treatment) and adjuvant treatment (therapy used after the main procedure) are two protocols widely used in cancer therapy. Neoadjuvant therapy allows the reduction of tumor mass, which permits the use of conservative surgery in cases where the size of the tumor is an obstacle. Adjuvant therapy, on the other hand, is responsible for increasing the patient's overall survival and reducing mortality rates due to the disease. Thus, the present study aims to continue preclinical studies with the molecule, evaluating the neoadjuvant and adjuvant therapeutic protocols with LW-9 associated or not with doxorubicin in a murine model of mammary tumor. This is an essential step so that the research can advance, in the future, to clinical trials. (AU)