Activity Detail
Christmas Lecture
How Tumors Outsmart Therapies and Inspire New Precision Strategies
Ana Ruiz
Despite remarkable advances in cancer research, therapeutic resistance continues to challenge the long-term efficacy of targeted treatments. Resistance often comes at a biological cost, revealing new vulnerabilities that can be exploited therapeutically. Understanding the molecular underpinnings of resistance is therefore essential to unlock new precision strategies in oncology.
Their group is dedicated to uncovering the molecular mechanisms that govern the efficacy of targeted therapies in breast cancer, with a particular focus on the HER2-positive subtype, where resistance to HER2-targeting agents significantly compromises clinical outcomes. In this context, they are investigating biomarkers of response and resistance with a particular interest in aberrant glycosylation. While altered glycosylation in cancer is known to influence critical aspects of tumor progression such as metastasis and immune modulation, its impact on the efficacy of HER2-targeted therapies remains largely unexplored.
To address this, and recognizing that tumors are much more than just cancer cells, they employ an integrative approach combining clinical datasets, mouse models, cancer-immune 3D co-culture spheroids, CRISPR screens and high-content live-cell imaging. This allows them to investigate how altered glycosylation and other molecular suspects shape therapeutic outcomes to HER2-targeting therapies, including antibody-drug conjugates (ADCs) such as the promising trastuzumab-deruxtecan.
In this lecture, Ana will discuss how tumors evade targeting therapies through rewiring of their signaling networks and hijacking of immune responses. She will also highlight the importance of modeling tumor architecture and cellular interactions, particularly in 3D systems, to better understand therapeutic efficacy. By addressing these aspects, the field is moving towards a new era of targeted therapy development, where ADCs and other advanced strategies can transform resistance from a barrier into an opportunity for therapeutic innovation.