Precision Medicine for Tailored Treatments

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 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.

Our Goal is Discovering Precision Medicines and Finding a Mechanistic Hypothesis Before Entering the Clinic

We have generated technologies that focus on robust in vitro assays to identify the mechanism of drug candidates. Our technologies provide in vitro proof of concept which facilitates the design of in vivo studies and clinical trials.

Precision Medicine flowchart

Oncolines™

Broad cell-based activity of drugs can be assessed via proliferation assays in a panel of cancer cell lines. 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 is 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 by Libouban et al., 2017. The Oncolines™ cell lines are also the basis of drug combination screens, as described by Uitdehaag et al. 2015.

oncolines.com

ResidenceTimer™

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 relationship 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).

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