Discovery of Precision Oncology Drugs
Finding the Informed Route With In Vitro Biochemical Assays, for Proof of Concept to Clinic
Oncolines is a precision medicine services company in oncology and cancer immunotherapy. Our Clients are clinical and preclinical biopharma companies and academic institutions that seek differentiation for their drugs and drug candidates. By cancer cell panel profiling, we identify predictive drug response biomarkers, new disease indications and synergistic drug combinations. We present results in a unique interactive reporting format to facilitate easier and faster interpretation of results. To investigate the mechanism of action of compounds, we perform gene and protein expression analysis, DNA and RNA sequencing. We generate, process, analyze, visualize, and interpret complex data. We present meaningful data and discuss them with our Clients. With our extensive reference compound database we identify differentiation and mechanism of action. We share our knowledge in cancer drug development. We help cancer researchers to move their projects to the clinic faster.
Reproducible Results, Short Timelines, Swift Communications
We provide high quality results with a short delivery time. Direct contact between our staff and sponsors results in efficient scientific and technical support. We provide cost-free consultation on next steps in research if desired by the sponsor.
Identification of Patient Stratification Markers
Oncolines® Profiling consists of the parallel profiling of drug candidates on a panel of 102 human cancer cell lines. The cancer cell lines are from diverse tumor tissue origin and have been characterized with regard to the mutation status of cancer genes and by gene expression analysis. Clients of Oncolines can order full panel profiling studies or cherry pick cell lines from the panel based on specific characteristics, such as tumor origin, gene mutations, or expression of certain cancer genes. The drug sensitivity of the Oncolines® cancer cell lines is determined in cell proliferation assays and correlated to the cancer gene mutation status of the cell lines. This yields novel candidate drug sensitivity biomarkers (Uitdehaag et al., 2019 and 2014).
These biomarkers are used as selection markers for patient stratification (Zaman et al., 2017), while the drug sensitivity fingerprint of compounds in Oncolines® is used for comparative analyses with other anti-cancer agents (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 (Uitdehaag et al., 2015).
In-Depth Analysis of Biological Mechanisms and Pathways
With flexible and tailored assay development we can focus on the biological pathways of interest. A wide range of cancer cells, immune cells and primary patient material are at our disposal. The proof-of-concept studies will boost the science of your projects.
Biochemical Characterization of Inhibitor-Target Interaction
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 ResidenceTimer™, for 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).
Quality. Flexibility. Short Turnaround Time.
References
Kooijman et al. (2022) Comparative kinase and cancer cell panel profiling of kinase inhibitors approved for clinical use from 2018 to 2020. Frontiers in Oncology, 12:953013.
Uitdehaag et al. (2019) Combined cellular and biochemical profiling to identify predictive drug response biomarkers for kinase inhibitors approved for clinical use between 2013 and 2017. Molecular Cancer Therapeutics, 18 (2):470-481.
Uitdehaag et al. (2014) Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use. PLOS ONE, 9 (3):e92146.
Zaman et al. (2017) TTK inhibitors as a targeted therapy for CTNNB1 (β-catenin) mutant cancers. Molecular Cancer Therapeutics, 16 (11):2609-2617.
Uitdehaag et al. (2016) Cell panel profiling reveals conserved therapeutic clusters and differentiates the mechanism of action of different PI3K/mTOR, Aurora kinase and EZH2 inhibitors. Molecular Cancer Therapeutics, 15 (12):3097-3109.
Libouban et al. (2017) Stable aneuploid tumor cells are more sensitive to TTK inhibition than chromosomally unstable cell lines. Oncotarget, 8 (24):38309-38325.
Uitdehaag et al. (2015) Selective Targeting of CTNNB1-, KRAS- or MYC-Driven Cell Growth by Combinations of Existing Drugs. PLoS ONE, 10 (5):e0125021.
Uitdehaag et al. (2017) Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity. Journal of Molecular Biology, 429:2211-2230.
Willemsen-Seegers et al. (2017) Compound Selectivity and Target Residence Time of Kinase Inhibitors Studied with Surface Plasmon Resonance. Journal of Molecular Biology, 429:574-586.
Grobben et al. (2020) Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158. Journal of Structural Biology: X, 4:100014.