HER2-positive breast cancer is one of the most aggressive and challenging subtypes due to its high proliferative rate, intratumoral heterogeneity, and resistance to conventional therapies. Although Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, has proven effective in patients refractory to monoclonal antibodies, its clinical application is limited by poor oral bioavailability, rapid hepatic metabolism, and gastrointestinal and hepatic adverse effects. In this context, aptamers have emerged as innovative tools for targeted drug delivery. Among them, AS1411, a G-quadruplex aptamer with high affinity for nucleolin overexpressed in tumor cells, represents a promising strategy to improve therapeutic selectivity and reduce systemic toxicity.

This study aims to evaluate, through computational approaches, the interaction between Lapatinib and the AS1411 aptamer, focusing on conformational stability, binding affinity, and targeting capacity toward HER2. Advanced in silico methodologies will be employed, including molecular docking (AutoDock Vina and HADDOCK) and molecular dynamics simulations (GROMACS), combined with binding free energy calculations, RMSD, RMSF, and radius of gyration analyses under simulated physiological conditions.

It is expected that the AS1411–Lapatinib complex will exhibit stable and specific binding, enhancing selective internalization into HER2-positive cells and optimizing the inhibition of PI3K/AKT and MAPK signaling pathways associated with tumor proliferation and therapeutic resistance. These anticipated findings support the potential of this system as a drug repurposing and targeted delivery strategy, with clinical implications in radiosensitization and the design of personalized therapies aimed at improving therapeutic efficacy while minimizing adverse effects in patients with HER2-positive breast cancer.

María Fernanda Barrientos Nava is a Master’s student in Biochemical Engineering at the Instituto Tecnológico de Celaya, México. She earned her degree in Biotechnology Engineering from the Universidad Politécnica de Guanajuato (2016–2021), completing her undergraduate thesis on the effect of cytokinins in Solanum lycopersicum L. infected with Candidatus Liberibacter solanacearum, under the supervision of Dr. Víctor Manuel Zúñiga Mayo (CONACYT).

Her professional background includes roles as Design and Development Technician at Ricap S.A. de C.V. (2021–2024), QC Technician at Sensient Flavors LATAM, and Molecular Biology Technician at Colegio de Posgraduados, where she gained solid experience in product formulation, statistical analysis, process optimization, and advanced laboratory techniques such as PCR, electrophoresis, and bioreactor scaling.

In addition to her academic and professional experience, she has pursued continuous training through specialized courses and certifications.She recently obtained a BioScience certification in Cell Signaling Pathways, completed a certification in Molecular Docking Applications, and attended a minicourse with GenomicsTracks Solutions focused on transcriptomic data analysis from scratch. She also strengthened her skills through workshops in pharmacovigilance, analytical techniques (HPLC, GC–MS), food biotechnology, and biostatistics.

Her current research centers on computational oncology, applying docking and molecular dynamics to evaluate the AS1411 aptamer– Lapatinib complex in HER2-positive breast cancer. Her goal is to contribute to targeted therapies, radiosensitization strategies, and drug repurposing approaches to overcome therapeutic resistance  in  aggressive  cancer  subtypes