The development of patient-derived xenografts (PDXs) from breast cancer patients is paving the way for more precise cancer treatments, particularly for populations previously underrepresented in such research. A recent study has reported the first breast cancer PDX models originating from South American women, aimed at enhancing the efficacy of treatment by tailoring it to the genetic and biological characteristics of this group.
Breast cancer is the leading cause of cancer-related deaths among women globally, with various subtypes presenting unique biological behaviors and treatment responses. The study, conducted by researchers at Instituto de Biología y Medicina Experimental (IBYME) and other institutions across Argentina, established eight PDX models derived from surgical fragments of breast tumors from local patients. These models are significant because they bring the total PDX collection from South America to the forefront of cancer research, filling the gap created by the growing need for diverse genetic backgrounds in cancer studies.
Researchers made use of surgically removed tumor fragments from women undergoing surgery for breast cancer to generate their PDX models. The process involved grafting pieces of the tumor tissue onto immunocompromised mice. These xenografts then underwent extensive analyses to study mutation profiles, hormonal receptor expressions (such as estrogen and progesterone receptors), and their responses to varied therapeutic options.
Among the established PDXs, notable findings included the response patterns to existing drugs like trastuzumab and tamoxifen. One specific model, BC-AR685, displayed sensitivity to mifepristone, tamoxifen, and palbociclib, contributing to the growing data linking drug responsiveness to specific genetic mutations. The inclusion of hormonal receptors such as androgen (AR) and glucocorticoid (GR) provides additional avenues for treatments, especially for triple-negative breast cancer (TNBC) variants, which often lack effective targeted therapies.
Previous studies have shown discrepancies between ethnic populations when it relates to cancer genomics and responses to treatments, underscoring the necessity for this South American PDX collection. The transverse benefits of this research extend beyond regional patient care contexts, signalling the importance of diverse PDX models to predict more accurately treatment outcomes based on distinct genetic backgrounds.
The characterization of the PDXs covered not just the response to initial treatments, but also the molecular analyses through whole exome sequencing, providing insights on the mutational landscapes present within the established models. The identification of mutations such as PIK3CA (C420R) hints at pathways influencing tumor growth responses, potentially guiding future treatment strategies for patients exhibiting similar genetic markers.
Looking forward, the creation of these models could have far-reaching applications not only for drug testing but also for the exploration of treatment combinations aiming to overcome resistance, particularly relevant for endocrine-resistant breast cancer cases. The urgency for effective breast cancer management continues to grow, and studies like this one play necessary roles, driving communities toward enhanced precision medicine approaches.
The broader implication of this work brings hope not just to South American patients but also to the international cancer research community, urging investments toward creating genetically diverse biobanks and PDX collections. Wit the implementation of these new models, the field can expect advancements not just in breast cancer treatments but potentially for other cancers, significantly improving patient outcomes overall.