Discover how XenoSTART’s clinic-to-bench pipeline delivers more clinically relevant PDX models, real-world patient data, and accelerated drug development.

Patient-derived xenograft (PDX) models provide the most accurate way to mimic clinical tumor characteristics and behavior in preclinical studies. By directly transplanting tumor tissue from patients into immunodeficient hosts, resulting PDX models preserve the original human tumors’ cellular architecture and molecular heterogeneity, enabling drug developers to test preclinical drug candidates in a clinically relevant model system.

Yet, the value of a PDX model for preclinical research depends on its quality and ability to capture characteristics of a modern patient population for which new, approved therapies will be utilized. Many public and private PDX collections currently exist with initial samples collected from various sources which may or may not be representative of today’s patients and their treatment therapies. The “clinic to bench” flow of cancer samples from hospitals, community practices, and clinical sites to preclinical researchers for PDX generation and investigational drug efficacy testing is vital for the creation of relevant models to appropriately evaluate next generation therapies.

In the following blog, we discuss the history and evolution of PDX models including sample sourcing, modeling, and utility. We focus on the value proposition of a “clinic-to-bench” pipeline describe drawbacks and considerations from modern-day PDX model banks, and demonstrate how close collaboration between clinical sites – especially ones testing investigational therapies on Western populations – and PDX model developers can streamline drug development. Through continuous collection of present day or modern cancer samples and longitudinal patient data, researchers can better understand new therapies, gather detailed medical and treatment histories, and interact directly with principal investigators (PIs). This approach helps ensure that newly generated PDX models accurately capture current tumor biology and evolving patient treatment needs.

Where Does Tumor Tissue for PDX Models Come From?

When selecting a PDX model from academic or commercial databases, researchers often focus on genetic markers, tumor type, or treatment history. However, one of the most critical – and often overlooked – determinants of a model’s utility lie in the upstream process: How and where the original tumor tissue was sourced. The quality, diversity, and relevance of a PDX model are deeply tied to the clinical context of the tissue donor, making sourcing a cornerstone of the translational value of a model.

Over the years, many academic and non-profit institutions have curated PDX collections through specialized research studies targeting specific cancer types. Notable examples include the Greehey Children’s Cancer Research Institute, EurOPDX consortium, National Cancer Institute’s (NCI) Patient-Derived Models Repository (PDMR), and St. Jude Children’s Research Hospital Patient-Derived Orthotopic Xenografts (PDOX) Biobank. These collections have great value in the preclinical R&D space, yet are constrained by clinical scope and geographic location, often derived from a handful of hospitals and shaped by the standards of care at the time of collection. As a result, researchers may encounter models with “outdated” clinical relevance, limited demographic diversity, or incomplete patient metadata.

To address these limitations, PDX biobanks are attempting to bridge these gaps, offering more standardized metadata and more diverse patient populations. The previously mentioned PDMR and St. Jude’s PDOX biobank, along with many commercial vendors, offer access to models that are richly annotated with clinical, genomic, and histopathological data. Some commercial vendors also provide sophisticated search platforms and expanded tumor libraries for greater findability and accessibility by drug developers. However, gaps remain in terms of donor clinical histories, ongoing investigator collaboration, and continued access to patients throughout their clinical journey. To ensure meaningful preclinical insights, researchers must not only consider tumor characteristics but also critically assess the origin and documentation of each PDX model, pushing for improved sourcing standards that align with modern therapies and diverse patient populations that are of the greatest interest to drug developers.

4 Key Considerations for PDX Model Collections

While PDX collections may fast-track drug development by providing ready-to-use, validated models, there are several factors to keep in mind that may limit the applicability of certain PDX model collections to your drug development efforts. Recognizing these factors can help you make a more informed decision about whether a model may be suitable for your preclinical R&D campaign.

Here are some key factors that impact the translational value of PDX model collections:

• Focused Scope: Many collections focus on particular research aims, cancer types, or geographical origins. This restricted diversity can limit the preclinical utility of available models. For instance, the prevalence of models derived from Eastern populations in commercial collections raises concerns about their representation of Western patient populations with different treatment histories, genetic profiles, lifestyles, and diets.

• Evolving Treatment Landscape: PDX collections may span multiple decades and could be considered “dated,” not reflecting today’s patient demographics or the latest treatments (e.g., checkpoint inhibitors, KRAS mutant inhibitors, CAR T-cell therapies, etc.).

• Single, Early-Stage Biopsies: Many collections further restrict their translational value by failing to capture the dynamic nature of cancer progression, treatment resistance, and metastasis. They rely on a single biopsy from a single patient, offering only a snapshot of the patient’s cancer. In addition, biopsies are often taken from newly diagnosed patients as it generally provides the greatest amount of tissue. This “snapshot” of a tumor is at a single moment in time, before they receive any kind of treatment.

• Lack of PI Involvement or Guidance: Without the active and ongoing involvement of principal investigators, critical patient details and trends (treatment history, evolving disease progression, and genetic profiles) can be missed, reducing the translational value of resulting PDX models.

To enhance the translational value of PDX models, several key adjustments are necessary. First, expanding the diversity of PDX collections to encompass a broader range of cancer types, patient demographics (including geographic and ethnic diversity), and treatment histories is crucial. Incorporating current patient populations and contemporary treatment paradigms will also increase their relevance to modern drug development. In addition, emphasizing longitudinal sampling of patients that have received first-line therapy, experienced relapse or treatment resistance, moved on to subsequent treatment lines, and throughout the rest of their clinical journey will provide more translational value than early “one-off” tumor biopsies. Lastly, facilitating stronger and more integrated collaborations between researchers and clinical sites is essential for enabling longitudinal sampling and ensuring the ongoing availability of detailed patient data and principal investigator guidance.

XenoSTART’s Clinic-to-Bench Pipeline

At XenoSTART, we provide access to the world’s most extensive collection of pre-treated PDX models sourced through our global specimen acquisition program. The program, The START Center for Cancer Research (“START”) operates as the clinical division of XenoSTART, running early-phase clinical sites across the U.S. and Europe for pharmaceutical sponsors. 

By continuously collecting new and diverse patient-derived cancer samples from Western populations, detailed medical and treatment histories, and rich molecular data, we ensure our PDX models align with contemporary therapies. Moreover, START’s ongoing expansion of clinical sites worldwide offers broader access to different tumor types, genetic backgrounds, and ethnicities. 

The Benefits of Partnering with The START Center for Cancer Research for your Oncology Drug Development Program

By leveraging START’s clinical expertise and the “clinic-to-bench,” pipeline, XenoSTART empowers researchers and pharmaceutical partners to advance drug discovery with PDX models that are highly relevant to today’s clinical landscape and patients. This streamlined clinic-to-bench pipeline reduces risk, enhances translational accuracy, and accelerates the pathway from bench to bedside.

Ready to tap into the industry’s largest collection of clinically relevant PDX models?

Contact us to learn how XenoSTART can bring your preclinical research program to the next level.