What’s the alternative to Xenograft models in Oncology?
There is a growing need for novel therapeutic treatments against cancer to help tackle the rising prevalence. Unfortunately, oncology drug attrition rates during clinical development remain high. Having human-relevant PK and PD information available earlier in drug development could help reduce attrition.
Accurately predicting the response of tumors to human pharmacokinetic (PK) profiles in vitro is challenging and modeling human tissue-specific biology in xenograft animal models can give rise to poor clinical translatability. Poor correlation between preclinical PK and pharmacodynamics (PD) parameters and clinical studies is one reason for the high drug failure rates.
Our solution
The in vitro assay behind our Oncology Contract Research Services uses a proprietary microphysiological system (MPS), the PhysioMimix™ PK, that administers time-varying drug concentrations to human 3D tumor models, exposing them to a PK profile rather than static concentration. Drug combinations, personalized medicine, dose schedules, and PK/PD relationships can be tested in this manner to explore a greater experimental space than possible using xenograft models.
Until now the effects of PK could only be studied in silico or in vivo. The PhysioMimix PK oncology assay enables the relationship between PK, PD, and efficacy to be studied at scale in the lab, for any 2D or 3D cell line, organoid, or patient-derived tumor model.
Understanding and optimizing the PK/PD/efficacy relationship is key to developing new oncology drugs. By addressing a workflow gap, our PK assay provides a unique means to explore these relationships in vitro. This approach lowers the cost and time to define the relationship, supporting improved drug discovery success rates.
Studying PK/PD relationships in oncology
Limitations of current techniques
- PK/PD relationship can only be tested preclinically in animal models (xenograft)
- Non-human PK profiles are often different from human PK profiles, stimulating different responses
- In silico predictions can only be validated in animals or clinical studies
- Optimization of drug combinations and dose schedules requires extensive animal studies
- Animal models and patient-derived materials for studies are large and costly
Advancements with PhysioMimix OOC
- Test predicted PK/PD relationships earlier in drug discovery
- Directly compare animal and human PK to understand translatability to clinical studies
- Test in silico predictions and build confidence
- Explore multiple possible combinations or drug dose schedules in vitro ahead of preclinical animal studies
- Multiple models can be tested within a single well plate, allowing for a cost-effective way to interrogate different conditions
Uniquely and rapidly discover the most efficacious novel treatments
Recapitulate in vivo or in silico drug PK profiles to create bespoke treatment regimens and monitor different therapeutic responses to determine effects on tumor biology. Multiple drugs can be combined to treat each tumor group/type, dosing e.g. BID (twice daily), QD (once daily), or Q.week (once weekly).
Recapitulate clinical efficacy in vitro
Detect distinct responses to mono- or combination therapies in 3D tumor models. Following exposure to clinically relevant drug dosing regimens for multiple weeks, tumors are assessed for cell health and specific drug response biomarkers (e.g. DNA damage – green).
Access our Oncology Service
Access the power of PhysioMimix PK via our CRO Service to perform experiments that wouldn’t otherwise be possible. Through a collaborative approach, our experts work with you to plan and execute your study.
Bespoke projects are carried out by our dedicated team of scientists in our CRO facility providing you with actionable data within weeks.
Featured resources
Scientific publications
A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models
Posters
In vitro assessment of combination dosing regimen with in vivo-like pharmacokinetic concentration profiles enabled by a microfluidic addition and removal device