Despite showing promising activity in pre-clinical testing, 85% of drugs fail in the early clinical trials and only half of the drugs that enter Phase III became approved for clinical use. This data demonstrates that pre-clinical screening approaches currently used mainly based on established 2D cell lines, are characterized by a limited ability to correctly select for clinical effective drugs, probably due to the fact that these models may pose an over-simplification and underestimation of the (epi)genetic diversity of the individual cancer patients.
Considering that in vivo tissues are integral 3D structures, the use of 3D in vitro techniques to test drug efficacy allows a more accurate mimicry of the native cancer tissue since it is possible to preserve physiological morphology and heterogeneity.
Moreover, the availability of hetero-cellular tumor spheroids allows the application of this model not only to the study of drugs directly targeting tumor cells, but also to compounds acting on the cells from the tumor microenvironment such as immune, endothelial and stroma cells.
The application of 3D cultures allows researchers and pharmaceutical companies to test newly developed compounds in a system that is closer to the physiological situation compared to standard 2D models, increasing the probability of success in translating the results into animal and human trials.
IN VITRO TOXICITY ASSAYS
Drug toxicity is the major reason for withdrawal of approved drugs from the market. While toxicity testing has been traditionally completed in the preclinical phase, it has become obvious that a failure at this stage results in significant setbacks and economic loss.
To address the challenge, cpo offers a panel of in vitro toxicology assays that are designed for the early stages of drug discovery utilizing cutting-edge technologies, such as semi-automated 3D cell culture screenings. By working with us, you have immediate access to these assays without major capital and time investment to establish these assays in-house. Designed with you project's needs in mind, our assays are valuable for evaluating compound liabilities early in the drug discovery process.
LARGE MOLECULE BIOLOGICALS
The types of therapeutics used to treat cancer are the most diverse among therapeutic areas. Of growing success and interest has been large molecule therapeutics for oncology, especially humanized monoclonal antibodies (mAbs). MAbs are generally targeted to cell surface receptors, or the ligands of these receptors, to block various oncogenic hallmarks (e.g., uncontrolled cell proliferation). PD3D™ services can help profile cell surface antigen expression for a mAb's target and identify drug responsiveness in the same assay.
Druggable epigenetic modulators undergo oncogenic mutation and are seen as attractive therapeutic targets. However, inhibition of some epigenetic targets results in a significantly delayed drug response that is not revealed by conventional, short term cell growth assays. To address this issue, we have established 2D and 3D assays with extended duration to yield robust response data. Of course any other slow-acting therapeutics are likely benefit from these extended protocols.
Cancer is a multi-dimensional disease driven by genetic instability and selective pressure to continue to persist. As such, an ever changing tumor presents a formidable challenge to effectively treat. Given this challenge, a strategy aiming to eliminate multiple traits and/or to prevent the tumor from developing resistance mechanism to circumventing treatment is essential. To support this, combinations of therapeutics (small-molecules or biologics) are tested on PD3D™ cell lines in a dose response matrix.