Precision Medicine is tailored to the individual patient instead of a one‐drug‐fits‐all model. It has been very successful in the area of inhibitors targeting BRCA-mutant cancers with PARP inhibitors and specific oncogenic kinases, such as EGFR, BRAF, ALK and BCR-ABL. There is tremendous potential for more Precision Medicine. By finding exquisitely sensitive cancer subtypes and developing selective therapeutics, the therapeutic efficacy of a drug or drug combination can be enlarged, leading to a much greater chance of success in clinical trials.
It is our mission at NTRC to help you with Precision Medicine and to find a mechanistic hypothesis before entering the clinic. We have generated technologies that focus on robust in vitro assays that help you identify the mechanism of preclinical and clinical drug candidates. Our technologies provide in vitro proof of concept which facilitates the preparation of in vivo studies and clinical trials.
The cancer cell lines in the Oncolines™ panel are from diverse tumour tissue origin and have been characterized with regard to the mutation status of more than hundred cancer-causing genes and by the expression of more than eighteen thousand genes. The drug sensitivity of the cell lines is determined in cell proliferation assays and correlated to the cancer gene mutation status of the cell lines, yielding novel candidate drug sensitivity biomarkers as shown by (Uitdehaag et al. 2019).
These biomarkers are used as selection markers for patient stratification (Zaman et al., 2017), while the drug sensitivity fingerprint of compounds in the entire Oncolines™ cell panel is used for comparative analyses with other anti-cancer agents, described by (Uitdehaag et al. 2016), and for mechanism-of-action studies (Libouban et al., 2017). The Oncolines™ cell lines are also the basis of drug combination screens, as described by (Uitdehaag et al. 2015).
NTRC has a commercial license from the American Type Culture Collection (ATCC) for the 102 cell lines in the current panel. Clients of NTRC order either full panel profiling studies or cherry pick cell lines from the panel based on specific characteristics, such as tumour origin or expression of certain cancer gene mutations.
Precision Medicine also concerns the precise targeting of your compound. Selective molecular drug-target interactions decrease the likelihood of off-target toxicity. The optimization of structure-activity relation is facilitated by a variety of assays, such as the determination of the target residence time of a drug on its target (Uitdehaag et al., 2017). The longer the residence time, the longer the target is inhibited. The biochemical and kinetic selectivity of inhibitors form a basis for differentiation of drug candidates (Willemsen-Seegers et al., 2017). Further mechanistic understanding of the interactions can be provided by looking at the thermal stability of a protein in the presence and absence of a compound and resolution of drug-target crystal structures (Grobben et al., 2020).
We deliver reproducible results that are adapted to your specific needs with a short delivery time. Direct contacts between the sponsor and our staff results in efficient scientific and technical support. We provide cost-free consultation on next steps in research if desired by the sponsor.