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2 minute read
The landscape of oncology research and the quest for better treatments have intensified with the advent of precision medicine introducing more targeted agents with higher efficacy and lower toxicity compared to traditional chemotherapy. In personalized medicine, where tailored treatments are revolutionizing patient care, understanding drug resistance mechanisms is key to developing more effective therapies. This blog takes a deep dive into pre-treated patient-derived xenograft (PDX) models, explaining what they are and how they are employed in preclinical studies to combat resistance to standard of care drugs, ultimately leading to better patient outcomes.
Refining Precision: PDX Models in a Nutshell
PDX models involve the transplantation of human cancer tissue into immunodeficient mice for in vivo growth and expansion. The resultant 'model' is a living tumor system that retains molecular and cellular characteristics closely resembling those of the original patient tumor.
Compared to traditional cancer cell line models, PDX models are superior avatars as they capture the heterogeneity and microenvironmental cues found in human tumors. This fidelity allows for a more accurate predictive platform to assess drug responses in preclinical oncology research.
Unveiling Resistance: The Power of Pre-treated PDX Models
In the quest to outwit cancer, the central challenge has always been predicting and overcoming therapeutic resistance, which often arises after initial treatment with standard of care drugs. Pre-treated PDX models are established from tumors from patients that have previously been exposed to treatments, thus embodying resistant tumor phenotypes that can mimic clinical presentations.
The use of PDX models after exposure to specific lines of chemotherapy, hormone therapy, or targeted drug regimens reveals a wealth of insights into how these tumors adapt, evolve, and evade the therapeutic effects. This critical approach allows researchers to identify the genetic and molecular determinants of resistance and devise strategies to combat them.
Pre-treated PDX Models at Champions Oncology
Champions’ highly characterized biobank includes over 1,000 tumor models across 60+ tumor types derived from advanced stage primary and metastatic patient tumors pre-treated with a plethora of therapies including the latest generations of targeted antibodies and small molecules, immune checkpoint inhibitors, ADCs, bispecific antibodies, and even experimental therapies currently undergoing clinical trial.
Our pre-treated models can be easily identified in Lumin, where you can select models of interest to you based on clinical and molecular characteristics, and draft a PDX cohort for your next study.
With extensive longitudinal clinical annotations and industry-leading multi-omic and multi-modal characterization, Champions' pre-treated tumor models allow for testing therapeutic agents in systems that closely mirror the clinical trial patient population significantly derisking the drug development process.
Transforming Resistance to Resilience in Research
Pre-treated PDX models have already catalyzed groundbreaking advancements in oncological research. For instance, studies have utilized these models to identify secondary oncogenic events that drive drug resistance and to develop combinatorial therapies that prevent or even reverse drug insensitivity.
One of these studies is highlighted in our case study "Using Champions’ patient-derived xenograft (PDX) models for preclinical validation of HER2-specific small molecule inhibitors" where tucatinib is used as a single agent or in combination with trastuzumab in a selection of HER2-amplified PDX models, both pre-treated and naïve, showing tumor inhibition in trastuzumab-resistant models.
The data derived from pre-treated PDX models can be integral in informing personalized treatment strategies for cancer patients.
The Future of Research and Care in Oncology
The implications of utilizing pre-treated PDX models are not just confined to the benches of research labs. These models have the potential to significantly impact the course of clinical trials, where they can serve as powerful tools to validate therapeutic responses and study mechanisms of drug failure in a more controlled environment.
Investigating drug resistance in PDX models allows for a more systematic and accelerated approach to drug development. New compounds can be tested on pre-treated PDX models to evaluate their potential benefits, potential interactions with existing therapies, and their ability to overcome resistance, ensuring a fast track to clinical trial.
By providing a more accurate representation of human tumors and treatment responses, pre-treated PDX models bridge the gap between bench-side discoveries and clinical applications. This synergy is crucial in ensuring that the most promising treatments reach patients in a timely and effective manner.
