In a groundbreaking advancement for cancer research and personalized medicine, scientists in China have successfully established an extensive library of patient-derived xenografts (PDXs) sourced from gastrointestinal cancers. This pioneering development, recently detailed in BMC Cancer, represents a watershed moment for preclinical oncology research, placing unique emphasis on cancers that predominantly afflict the Chinese population, such as esophageal squamous cell carcinoma (ESCC). The creation of this comprehensive repository marks a considerable stride toward more targeted cancer therapies and accelerated drug development.
Patient-derived xenografts, or PDX models, involve the implantation of human tumor tissues directly into immunodeficient mice. These models maintain the histological architecture and genetic makeup of the original tumors far better than traditional cell lines, offering a more clinically relevant arena for testing therapeutic agents. The Chinese research team capitalized on this technique by transplanting over 1,000 surgical and biopsy specimens from patients with various gastrointestinal malignancies, including ESCC, esophagogastric junction adenocarcinoma (EGJAC), and gastric adenocarcinoma (GAC), into NOD/SCID mice, which lack adaptive immunity.
Between January 2013 and August 2015, the researchers conducted a comprehensive engraftment campaign, implanting the fresh tumor tissues subcutaneously into specialized mice and meticulously documenting engraftment rates and tumor growth dynamics. A total of 208 xenograft models were successfully established, representing an overall engraftment rate of approximately 20.8%, a notable achievement given the inherent challenges in PDX formation, especially within gastrointestinal tumors renowned for their heterogeneity and aggressive nature.
Diving deeper into the types of cancers, ESCC exhibited the highest engraftment rate at 21.2%, substantiating its clinical significance within the Chinese demographic due to higher incidence rates. EGJAC and GAC followed with engraftment rates of 16.9% and 10.9%, respectively. These variances underscore the biological complexities and tumor microenvironment interactions unique to each cancer subtype, influencing successful xenografting.
The latency period, or the time taken for implanted tumors to grow sufficiently in mice, varied amongst the cancer types. For the initial passage, ESCC xenografts established within an average of approximately 76 days, whereas EGJAC and GAC showed longer latency periods of around 90 and 85 days, respectively. Interestingly, during the subsequent passage, these latency periods reduced significantly across all tumor types, averaging around 52 to 55 days. This observation suggests an adaptation process where tumor cells, once acclimatized to the murine environment, exhibit expedited growth kinetics in subsequent passages.
Beyond mere establishment rates, the study unearthed noteworthy correlations between clinical and pathological factors and successful engraftment. In ESCC cases, variables such as patient gender, the type of specimen (biopsy vs. surgical tissue), and tumor differentiation significantly influenced engraftment outcomes. In gastric adenocarcinoma, factors including patient age, specimen type, tumor differentiation, and Lauren classification—a histological subtype categorizing gastric tumors as intestinal or diffuse—played influential roles. Such nuanced understanding emphasizes the importance of patient and tumor characteristics in PDX success rates, potentially aiding future patient stratification for personalized models.
From a clinical perspective, the team monitored patients over extended periods—46 months for ESCC and 64 months each for EGJAC and GAC—shedding light on the prognostic implications of xenograft formation. Intriguingly, patients with gastric adenocarcinoma whose tumor tissues yielded successful xenografts showed significantly poorer survival compared to those whose tumors failed to engraft. This finding aligns with previous literature suggesting that aggressive tumor biology is more amenable to PDX establishment, thereby providing a dual opportunity to study both tumor aggressiveness and responsiveness.
The establishment of this Chinese PDX library holds immense promise beyond academic achievement. It offers a robust platform for preclinical drug evaluation that more faithfully mimics human tumor biology. By encompassing tumor types prevalent in the Chinese population, the repository addresses a significant gap in cancer research where most existing PDX models are derived from Western populations, potentially limiting translational applicability.
Moreover, this repository facilitates personalized oncology approaches by enabling drug sensitivity testing on patient-specific tumor models. This approach could refine treatment regimens and identify novel therapeutic targets, ultimately enhancing patient outcomes. The ability to predict clinical responses based on PDX testing could transform current cancer care paradigms from empirical treatment choices to biology-driven precision medicine.
Establishing and maintaining such a biobank require overcoming considerable technical and logistical challenges, including tissue procurement, handling, and engraftment consistency. The success rate reported in this study reflects rigorous methodological optimization and a sustained commitment to creating a high-quality resource. The researchers’ choice of NOD/SCID mice underscores the necessity of immunodeficient hosts to facilitate human tumor growth, eliminating confounding by host immune rejection.
As this PDX library expands, it opens avenues for collaborative research endeavors at both national and international levels. The availability of well-characterized, genomically annotated PDX models could accelerate the validation of molecular targets and the development of next-generation therapeutic agents tailored to tumor-specific vulnerabilities.
Furthermore, this initiative underscores the importance of integrating clinical annotations with experimental models. Matching PDX data with detailed patient clinical information enriches the translational value of findings and fosters the discovery of biomarkers predictive of treatment response or resistance.
While the current focus centers on gastrointestinal tumors—given their significant morbidity and mortality in China—the framework established by this research sets a precedent for creating PDX libraries from other cancer types, fostering a broader understanding of cancer heterogeneity and treatment resistance mechanisms.
In synthesizing these efforts, this study contributes substantially to the global oncology research infrastructure. It aligns with the growing consensus that high-fidelity preclinical models are paramount to overcoming the translational gap that has historically hindered effective drug development.
In conclusion, the establishment of a Chinese PDX library from gastrointestinal cancers signifies a milestone in personalized cancer research. By capturing the biological intricacies of predominant local tumor types, this resource empowers researchers and clinicians with refined tools for therapy development and individualized treatment decision-making. This endeavor not only enhances scientific understanding but also holds the potential to directly impact patient care, offering hope for improved survival outcomes in a cancer-burdened population.
Subject of Research: Establishment and characterization of a patient-derived xenograft (PDX) library from gastrointestinal cancers prevalent in China, including esophageal squamous cell carcinoma, esophagogastric junction adenocarcinoma, and gastric adenocarcinoma.
Article Title: Establishment of a Chinese library of patient-derived xenografts from gastrointestinal cancers
Article References:
Liu, Y., He, W., Wu, Q. et al. Establishment of a Chinese library of patient-derived xenografts from gastrointestinal cancers. BMC Cancer 25, 1508 (2025). https://doi.org/10.1186/s12885-025-14845-y
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14845-y
Tags: China cancer researchdrug development accelerationesophageal squamous cell carcinomaesophagogastric junction adenocarcinomagastrointestinal cancer libraryimmunodeficient mouse modelspatient-derived xenograftspersonalized medicine advancementspreclinical oncology researchsurgical biopsy specimenstargeted cancer therapiestumor growth dynamics
