A Novel Dynamic Fluid Culture System Enhances Breast Cancer Organoid Growth for Faster Drug Sensitivity Testing
Researchers develop innovative organoid technology, paving the way for more efficient precision medicine applications.
Breast cancer remains the most common and deadly malignancy worldwide among women, ranking first for both incidence and mortality. Advancements in treatment often rely on chemotherapy, but traditional methods face significant challenges, including the time-consuming nature of drug sensitivity testing. Conventional organoid culture techniques for representing tumor behavior typically require over three weeks to establish, resulting in delays for patients awaiting personalized treatment responses.
To address this pressing need, researchers at Shanxi Provincial Cancer Hospital have pioneered a dynamic fluid culture system engineered to significantly accelerate the growth of breast cancer organoids. Their study, published on March 16, 2025, details how this innovative system optimizes nutrient supply necessary for the organoid development process.
The study's findings reveal how the fluidic system builds upon the traditional organoid "dome" culture method, which combines isolated cancer cells with matrix gel for 3D growth. The newly developed methodology effectively reduces the overall culture time without sacrificing tissue histology or drug sensitivity features. By ensuring continuous access to nutrients, the fluid culture maintained organoid viability over two weeks, demonstrating larger diameters compared to static controls across all tested samples.
Researchers developed organoids derived from three patients with invasive ductal carcinoma, cultivating them under fluidic and static conditions before evaluating viability and morphology. After 15 days, the study found the fluid-cultured organoids consistently showed higher viability than those grown under static conditions, indicating enhanced growth and metabolic activity.
Remarkably, immunohistochemical analyses confirmed both culture systems preserved the molecular characteristics of the original tumor tissue. The retention of drug susceptibility across different methods marks both methods as viable for future drug testing protocols. According to the authors of the article, "Our findings indicate similar pharmacological responses to drug treatments between organoids cultured under both methods." This consistency is promising for the future of precision medicine.
Looking beyond enhanced growth rates, the fluid culture system also incorporates mechanical effects from fluid shear stress believed to play role in the growth dynamics of these organoids. The innovative design leverages the principles of developmental biology, where vascular systems are understood to be necessary for tissue growth. The supply of nutrients predominantly occurs through passive diffusion in traditional static cultures, which limits the size and proliferation capacity of organoids.
Through rigorous experimentation, the team monitored changes across multiple time points, noting significant differences between the fluidic environment and both static cultures and another control group where medium was replenished daily. Notably, only the fluid-cultured organoids exhibited pronounced diameter changes and superior viability post-culture.
While the immediate benefits of this new system are clear, researchers anticipate broader applications for organoid technology within precision medicine. "The efficiency gained from the fluid culture method holds promise for translating this technology from the lab to bedside. It enhances our ability to provide timely treatment recommendations based on the individual tumor response," explained the researchers. With the increasing complexity of cancer treatments, accelerating the drug sensitivity process becomes imperative.
Despite positive findings, the study also highlighted challenges. After 30 days of culture, larger organoids showed signs of cell detachment and localized apoptosis. Researchers believe this response may occur due to the excessive size of the organoids and insufficient internal nutrient supply, reminiscent of problems faced by static cultures.
The loss of estrogen receptor (ER) and progesterone receptor (PR) expression during the culture period illuminates the need for continued research on possible signaling pathways involved, with aberrant activation of the NOTCH pathway suggested as potential factors.
This study is timely amid growing global breast cancer statistics and highlights how innovative organoid technology may serve as powerful tools for personalized cancer treatment. Shifting paradigms to improve dynamic culture systems could redefine approaches to drug screening and therapeutic efficacy studies, potentially leading to advances throughout oncology and beyond.