3D Biology: The paradigm shift in next-generation drug discovery [Interactive infographic]
Originally Published: April 19, 2023
The drug discovery landscape is changing
April 19, 2023 Bringing a drug to market has historically been time-consuming and costly, with many candidates failing in the first phase of clinical trials. Growing evidence suggests that screening compounds early in the process using traditional models – like animals and cell cultures propagated in 2D – may be a contributing factor.
Researchers are now navigating toward complex, human-relevant 3D systems like organoids, as they are believed to better represent how the body might respond to treatment.
Experience our interactive infographic as it takes you deeper into why the industry is embracing this next generation of drug discovery and the innovations supporting scientists in their 3D biology journey.
What is the Drug Discovery Paradigm?
3D biology is the next-generation of drug discovery – a transition away from 2D cell cultures and animal models to more biologically relevant 3D cell models and human systems.
Begin your journey from 2D to 3D biology within our latest blog as we show you what it takes to enter into this new drug discovery paradigm and how researchers worldwide are transitioning their compound screens away from 2D cell cultures and animal models to more complex, human-relevant 3D systems like organoids.
The revolutionary promise of 3D biology
Human-relevant models provide early insights into drug interactions with human cells, detecting efficacy and toxicity concerns pre-clinically. The emerging field of 3D biology is revolutionizing drug screening and disease understanding, offering a unique advantage in predicting human responses to new treatments.
The expensive and lengthy path of drug development
Despite billion-dollar investments, getting new drugs approved is still a lengthy and costly process, mainly due to high attrition rates. Traditional 2D cell cultures and animal models often fail to predict how drugs will perform in humans, leading to many potential drugs falling short during development.
A staggering 75% of research and development costs come from failures—funds spent on projects that initially seem promising but are later found ineffective, unsafe, or commercially unviable during human trials. It's clear that the drug development process needs a revolution, and organoids might be the key to achieving it.
Limitations of conventional cell models
Ethical consideration aside, traditional cell models in drug research – whether 2D cell lines, small animal models, or non-human primates – face translatability challenges that hinder their success in moving therapeutics from bench to bedside.
To address this, the Drug Discovery Paradigm leverages human-relevant model systems throughout drug discovery to improve clinical success rates and reduce dependency on animal models. Organoids are reducing the translatability gap by accurately predicting drug outcomes. Studies indicate that drugs failing on patient organoids in pre-clinical trials will likely fail in actual patients, while a high success rate will translate to effective patient outcomes.
Despite their potential, growing organoids can be labor-intensive and time-consuming, affecting scalability. However, automated cell culture technologies and assay-ready organoids are enhancing scalability to make their adoption more feasible.
Regulatory boost for organoids
Organoid technology
These miniature versions of organs are revolutionizing medical research with their unique capabilities. Brain organoids, for instance, provide invaluable insights into human brain development and neurological diseases, making them ideal for testing pharmaceutical drugs and studying genetic mutations. Intestinal organoids, with their accurate replication of the intestinal epithelium, are crucial for understanding cell biology, regeneration, and disease phenotypes related to the gut. Tumoroids, derived from patient tumors, are game-changers in cancer research, enabling personalized medicine by allowing researchers to analyze tumor biomarkers and screen for the most effective anti-cancer drugs. Lung organoids replicate the complex structure and function of the airway, making them perfect for drug screening and disease modeling in respiratory conditions.
Collectively, these diverse organoid types are paving the way for groundbreaking advancements in medical research and therapeutic development.
- Brain Organoids
- Breast Cancer Tumoroids
- Cardiac Organoids
- Colorectal Cancer (CRC) Organoids
- Intestinal Organoids
- Patient-derived organoids (Tumoroids)
- Pulmonary (Lung) Organoids
3 key organoid use cases
Because organoids so closely resemble their internal organ counterparts, they have proven to be an accurate 3D cell model for studying human disease, screening drugs, and testing potential therapeutics. They’re also an especially useful tool for precision medicine. For example, patient derived organoids can be generated from individuals with specific ailments and used to better understand disease, develop drugs, and customize personalized therapies.
DISEASE MODELING
Disease modeling is a cornerstone of biomedical research, offering systems that mimic the behavior of diseases in controlled environments to uncover their underlying mechanisms and test potential therapies.
While traditional models like 2D cell cultures and animals have limitations, organoids offer a reliable alternative by replicating human tissue complexity. This makes them ideal for studying diseases such as Alzheimer's, heart failure, and cancer. Organoids could also provide a more accessible solution for advancing rare disease research, potentially unearthing treatment for the 7,000 rare diseases affecting 400 million people globally, of which only 500 are actively studied.
DRUG SCREENING
High-throughput drug screening (HTS) revolutionized the 1990s by enabling rapid testing of multi-million-compound libraries using multi-well plates. The approach aimed to test every compound in an extensive library to find a few active ones, but the process was cumbersome and often failed to produce clinically relevant results.
Today, the shift from 2D models to advanced 3D biological models like organoids – combined with automation and AI technology – is enhancing the precision and relevance of HTS, making it possible to pinpoint the most promising drug candidates faster.
PDOs
Patient-derived organoids (PDOs), or tumoroids, are revolutionizing drug discovery and cancer research by offering human relevant models derived from individual patients' tumors. Generated from tumor biopsies or surgical samples, these 3D cultures maintain the molecular characteristics of the original tumors and exhibit cancer stem cell-like properties. This makes them invaluable for understanding patient-specific drug responses, analyzing tumor biomarkers, and screening for the most effective anti-cancer drugs. In challenging cancers like breast and colorectal cancer, PDOs have shown superior potential in precision medicine and high-throughput drug discovery applications, particularly when supported by automation, high-content imaging, and AI data analysis.
The challenges with organoids
Adopting 3D biology can present significant barriers, despite the promise of organoids offering greater predictability and more biologically relevant data than 2D cell models. However, understanding these challenges is the first step toward finding solutions to streamline processes and deliver safer, much-needed therapies to patients faster.
Radical innovation required
Embracing innovation in organoid technology is essential to revolutionizing drug discovery. By advancing protocols, leveraging automation, and incorporating the power of AI, we can improve accuracy, reduce costs, and accelerate drug discovery timelines.
Assay-ready Organoids
Through our 3D Ready™ Organoids and Organoid Expansion Service, we use proprietary bioreactor and bioprocess technology to produce high-quality, reliable PDOs at scale. This includes both assay-ready organoids from curated lines and the ability to expand proprietary organoid lines to meet specific research needs, providing consistent and high-quality human-relevant models for a variety of applications.
High-throughput, High-content Imaging
High-performance imagers play a crucial role in scientific research by providing the detailed, high-resolution images necessary for accurate data analysis and discovery. Our growing line of ImageXpress® high-content imaging systems offer impeccable image quality, speed, data richness, and analytical accuracy, so researchers can clearly visualize complex biological processes for greater insights.
Artificial Intelligence
IN Carta® Image Analysis Software is a powerful AI/ML software that revolutionizes image analysis and workflow efficiency for scientific research. Integrated into our automated cell culture system, it simplifies decision-making and enhances experiment accuracy by using images to ultimately inform consistent workflow automation, optimal cell culture feeding, and timely passaging events. The analysis capability also transforms complex images into easily interpretable results, inviting researchers to explore data, identify phenotypic changes, and uncover novel insights effortlessly without the need for deep data science expertise.
Automated Cell Culture
The CellXpress.ai™ Automated Cell Culture System alleviates repetitive tasks for organoid growth by integrating machine learning to manage complex feeding and passaging schedules. By combining advanced hardware and software technologies, this system automates and standardizes 2D and 3D cell culture processes, supporting scientists at every stage of organoid research and guiding them through workflows for iPSC, tumoroid, and adult stem cell-derived organoids. Its AI-powered software, efficient protocol development, and comprehensive event logging deliver reliable and reproducible results at scale.
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Organoid screening workflow
Implementing an effective, automated end-to-end workflow for advanced drug discovery depends on its ability to standardize and streamline the organoid development process, enhancing both throughput and accuracy. By integrating proven hardware and software solutions, an automated workflow can facilitate everything from 2D pre-culture of cells to high-content confocal imaging, and AI-enabled data analysis.
Our automated high-throughput screening solution offers protocols to manage cell plating, culture monitoring, media exchange, and compound treatment, covering both matrix-based and matrix-free organoid cultures. Comprehensive automation not only improves the precision of organoid assays but also allows for complex, quantitative analysis of cellular content and phenotypic changes, making it invaluable for drug screening and disease modeling.
Visit the Organoid Innovation Center
The Organoid Innovation Center demonstrates a fully-integrated solution that addresses the challenges associated with every step in the sample prep-to-report pipeline for assays performed on complex 3D biological models. An end-to-end solution standardizes the organoid development process with cell culture, treatment, and incubation, through to imaging, analysis, and data processing, delivering consistent, unbiased, and biologically-relevant results at scale.
Has this inspired you to explore a transition from 2D to 3D biology? To find solutions for your organoid challenges? Or to scale the work you’re already doing?
Our experts can help. Reach out to us today to get started.