Drug Combination Screening Assays

Combination therapies are essential in drug development in oncology, however the volume of possible combinations necessitates the use of in vitro and/or ex vivo screening platforms. Charles River has developed several relevant two-drug combination therapy screening formats to profile combinations of oncology drugs or developmental compounds for synergy or antagonism.

We offer combination studies as index analysis of fixed-ratio combinations according to Chou & Talalay, curve shift analysis according to Zhao, or matrix combination analysis based on Bliss Independence using 2D and 3D cell-based assays utilizing several hundreds of different oncology models, including PDX models.

Matrix combinations and evaluation based on Bliss Independence analysis allow you to study drug effects in a broad range of combination conditions.

 

Combination screening: the combination of Pimasertib (MEK1/2 inhibitor) and XL-765 (PI3K/mTOR inhibitor) tested in a 5x5 matrix layout in 2D monolayer culture shows synergistic effects in KRAS and PIK3CA double mutant DLD-1 cells.

Figure: The combination of Pimasertib (MEK1/2 inhibitor) and XL-765 (PI3K/mTOR inhibitor) tested in a 5x5 matrix layout in 2D monolayer culture shows synergistic effects in KRAS and PIK3CA double mutant DLD-1 cells, which confirms observation in literature (Temraz et al. Int. J. Mol. Sci. 16, 22976-22988, 2015; Haagensen et al. Brit. J. Cancer 106, 1386-1394, 2012).


Catching Patient Diversity In Vitro: PDX-based Assays in Oncology Drug Discovery

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Discover how scientists are using in vitro/ex vivo models to optimize immuno-oncological approaches and see how live-cell imaging and multiplex analysis can help us understand treatment efficacy.
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Combination therapy screening layouts are also available in the 2D assay or 3D assay platforms, and helps inform your strategy for in vivo testing.

Which assay is best for you?

Frequently Asked Questions (FAQs) about Combination Therapy Screening

  • What is combination therapy screening?

    Drug combination screening assesses the synergistic and antagonistic interactions between combined therapies, allowing us to identify combinations which will increase the efficacy of novel cancer therapies.

  • Why should I include combination therapy screening in my oncology drug development?

    Combination therapy can increase efficacy by targeting more than one molecular target, and help overcome resistance mechanisms. By including drug combination screening in vitro assays in your oncology drug development you can increase translation into the clinic.

  • What drugs should I include in my combination therapy screen?

    The assay format and drug combinations used in drug combination screening will depend on the mechanism of action, and on whether the drugs are mutually exclusive or non-exclusive. The most common combination in clinical trials is immune checkpoint inhibitors to PD-1 and CTLA-4, but drug combinations can include checkpoint agonists, cancer vaccines, other immunomodulatory agents, and more traditional options such as chemotherapy. Charles River’s oncology team can advise on suitable drug combinations to aid your drug development.