In recent years, patient-derived xenograft (PDX) models have emerged as one of the most powerful tools in personalized medicine, offering an unprecedented level of biological fidelity in cancer research. By implanting human tumor tissues into immunodeficient mice, PDX models preserve the complex architecture and heterogeneity of patient tumors, including oncogenes, tumor suppressors, and other critical molecular markers. These features make PDX models particularly advantageous in studying how tumors respond to specific treatments, thereby paving the way for more effective and individualized therapeutic strategies.
Patient-derived xenografts represent a powerful tool for personalized cancer treatment, with chemosensitivity testing offering vital insights into how individual tumors respond to chemotherapy. To begin a patient’s PDX testing and chemosensitivity xenograft testing the physician supplies Altogen Labs with a piece of resected living tumor, or biopsy (please contact info@altogenlabs.com for a formal quote and list of required documents). Note that standard PDX or chemosensitivity xenograft testing typically requires 2 to 3 months to complete, with associated costs ranging from $22,000 to $75,000 USD. Patient-derived xenograft with chemosensitivity xenograft testing is a preclinical model used to evaluate efficacy of different cancer therapies for a patient. PDX involves implanting human tumor tissue into mice, while chemosensitivity testing determines how effective specific drugs are against these tumors. The process spans 2-3 months, allowing time for tumor engraftment, drug administration, monitoring, and analysis of the therapeutic response. The $22,000 to $29,000 cost range reflects the complexity of the procedures, including animal care, tumor growth monitoring, drug administration, and specialized personnel needed to carry out these tasks. To learn more about xenotransplantation method please visit the xenograft science webpage. Xenotransplantation research applications are described at our xenograft applications resource. To learn more about in vivo xenograft testing services, please visit our services webpage. Available PDX models and standard PDX protocols are described at our PDX Models resource.
Standard 3-Step Xenograft Testing Process:
- Tumor tissues are implanted into multiple recipient immunocompromised mice and allowed to grow. Alternatively, the biopsy tissue is processed and cancer cell culture expanded and transformed (if necessary) to initiate xenotransplantation study.
- While tumor implant is growing, the patient should perform standard clinical tests and treatments as advised by physician. The patient’s physician will define the best xenograft testing strategy (PDX xenograft study, chemosensitivity tests, etc). Altogen Labs also offers a number of cancer characterization services, including protein (ELISA, WES, Western Blot) and mRNA expression (RT-PCR) analysis, biomarker expression and oncogene mutation analysis, IC50 assays, tumor cells drug response and resistance, as well as other types of tumor biology characterization and molecular analysis.
- During the xenograft study progression, our scientists will report study results as they become available to help physician in modifying treatment strategy as soon as possible. PDX and chemosensitivity testing will provide the patients with data as it become available to achieve best cancer treatment results via personalized therapy approach.
Patient-derived xenograft (PDX) models are revolutionizing personalized cancer treatment by providing a more accurate representation of human tumors. PDX models are created by implanting tumor cells or tissues from cancer patients into immunodeficient mice. This allows researchers to study the biology of the patient’s specific cancer in a living organism, preserving key characteristics such as tumor heterogeneity, growth patterns, and molecular profiles. One of the primary applications of PDX models is in chemosensitivity testing, which assesses how tumors respond to various chemotherapy drugs.
How PDX Models Work in Chemosensitivity Testing
Chemosensitivity testing using PDX models enables researchers and clinicians to evaluate the efficacy of different chemotherapeutic agents on a patient’s tumor before starting treatment. After establishing a PDX model from a patient’s tumor, researchers administer various drugs to the xenograft to identify which treatments are most effective in shrinking the tumor. Since PDX models retain the genetic and phenotypic properties of the original tumor, they offer a predictive platform for identifying drug responses and resistance mechanisms in real-time.
PDX Models: A Window into Tumor Complexity
Unlike conventional cell line models, which often fail to capture the full molecular landscape of tumors, PDX models retain the structural, genetic, and phenotypic heterogeneity present in the patient’s original tumor. This includes key features such as oncogene activation, tumor suppressor inactivation, somatic variants, and epigenetic modifications like DNA methylation. For example, in cancers driven by oncogenic mutations in genes like KRAS, TP53, or EGFR, PDX models allow for the study of how these specific mutations influence tumor behavior and response to targeted therapies.
Moreover, PDX models are valuable in conducting RNA sequencing (RNA-seq) and whole-exome sequencing to profile gene expression and identify somatic mutations, which can reveal actionable therapeutic targets. This allows for a comprehensive understanding of not only the genetic alterations driving the tumor but also the downstream transcriptional changes that may contribute to therapy resistance. Additionally, analysis of DNA methylation patterns in PDX tumors can provide insights into how epigenetic changes might influence tumor progression and response to treatment.
Types of Tumor Grafts and Their Role in Personalized Treatment
PDX models also offer the flexibility of using different types of tumor grafts, such as subcutaneous grafts, where tumor tissue is implanted under the skin, or orthotopic grafts, where tumor tissues are implanted in the same anatomical location as the original tumor (e.g., lung tumors implanted into the lungs). Orthotopic PDX models are especially valuable in studying the interactions between the tumor and its microenvironment, which is critical for understanding metastatic behavior and response to therapies that target both the tumor and its surrounding stroma.
These models can be further classified into different generations based on how many times they have been passaged in mice. Higher-generation PDXs may undergo genetic drift, but first-generation xenografts (PDX1) are particularly prized for their close molecular resemblance to the patient’s tumor. This high level of molecular fidelity in PDX1 models has been demonstrated across a variety of tumor types, including breast, colorectal, lung, and pancreatic cancers, making them an invaluable tool for biomarker discovery and drug sensitivity testing.
Superiority of PDX Models over Other Preclinical Models
One of the main reasons PDX models are considered superior to traditional cell lines or genetically engineered mouse models is their ability to maintain the tumor heterogeneity seen in patients. Tumor heterogeneity, which refers to the presence of diverse subclones within a tumor, plays a significant role in drug resistance. Cell lines, grown under artificial conditions, often lack this complexity, leading to results that may not translate well to human tumors.
Additionally, PDX models allow researchers to study the impact of somatic mutations in a patient-specific context, leading to the development of personalized treatment regimens. For example, PDX models can be used to screen various drugs, including chemotherapies and targeted therapies, to identify which treatments are most effective against a patient’s specific tumor profile. In cases where patients have tumors with actionable mutations (e.g., BRAF, EGFR, PIK3CA), PDX models enable testing of targeted therapies that inhibit these oncogenic pathways.
Advanced techniques such as RNA-seq and proteomics can be applied to PDX models to identify gene expression signatures associated with drug sensitivity or resistance. Furthermore, these models allow for longitudinal studies of drug resistance mechanisms, which can evolve over the course of treatment due to the selective pressures exerted by the therapy. This enables researchers to identify the emergence of drug-resistant clones and tailor subsequent therapies to target those resistant populations.
Predictive Power in Oncology
PDX models have proven their predictive power in numerous studies by closely mirroring the drug response observed in patients. This is particularly evident in their ability to predict chemotherapy responses and targeted therapy efficacy. For instance, in non-small cell lung cancer (NSCLC), PDX models have shown a strong correlation between the tumor’s response to EGFR inhibitors in the model and the patient’s clinical response. Moreover, these models are being used to test novel immunotherapies and combination therapies, providing a robust platform for preclinical drug development.
PDX models are increasingly seen as a more predictive platform for clinical outcomes compared to traditional in vitro models. They offer a high level of translational relevance, making them an invaluable tool for precision oncology. Through continued advancements in techniques such as single-cell RNA sequencing and CRISPR-based gene editing, PDX models will continue to drive forward personalized cancer therapy, providing better-targeted treatments with fewer off-target effects.
Clinical Significance
PDX models bridge the gap between traditional cell cultures and clinical trials by simulating how a tumor reacts to therapy in vivo. These models are particularly valuable for studying chemoresistant cancer subpopulations. By identifying which drugs a tumor is sensitive or resistant to, PDX-based chemosensitivity testing helps tailor personalized treatment regimens, potentially improving patient outcomes. This approach is especially beneficial for patients with aggressive cancers or those who have developed resistance to standard therapies.
Patient-derived xenograft models stand at the forefront of personalized medicine, offering a biologically accurate and predictive tool for understanding tumor behavior and drug responses. By preserving the genetic, molecular, and phenotypic complexity of human tumors, PDX models represent a powerful platform for developing and optimizing individualized treatment regimens that improve patient outcomes in the evolving landscape of cancer therapy.
In recent studies, PDX models have proven their worth in various cancer types, including ovarian, colorectal, breast, and non-small cell lung cancers. They enable researchers to explore new therapeutic combinations and test experimental drugs, accelerating the path toward precision medicine. However, challenges such as the high cost and time required to establish PDX models must be addressed to make this tool more accessible in clinical settings. As research advances, PDX models are likely to play an even more critical role in refining cancer treatment strategies and improving patient care outcomes.
References:
- Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer Link This study demonstrates how PDX models retain tumor heterogeneity, helping identify chemoresistant populations.
- Patient-derived xenograft (PDX) models of colorectal carcinoma (CRC) as a platform for chemosensitivity and biomarker analysis in personalized medicine The research highlights the use of CRC PDX models for testing chemosensitivity and analyzing biomarkers.
- A new model of patient tumor-derived breast cancer xenografts for preclinical assays Link This article introduces a breast cancer PDX model, comparing chemosensitivity screening results with patient tumor responses.
- A chemosensitivity study of colorectal cancer using xenografts of patient-derived tumor-initiating cells Read here The study compares the chemosensitivities of patient-derived xenografts with clinical responses in colorectal cancer.
- Patient-derived first generation xenografts of non–small cell lung cancers: Promising tools for predicting drug responses for personalized chemotherapy Read here This paper demonstrates the use of first-generation NSCLC xenografts for chemosensitivity testing.