Scientific Aims and Milestones
We will use a multidisciplinary approach that integrates clinical research with state of the art HTP screening of chemical libraries and target identification/validation technologies, including cell and molecular biology, transcriptomics, proteomics, computational biology and in vivo imaging techniques. We shall identify and characterize novel compounds that target critical pathways in cancer cells.
Aims:
- Reactivation of the key tumor suppressor p53
- Inhibition of the potent oncogene Myc
- Targeting cannabinoid receptors
- Prevention of tumor angiogenesis
Milestones:
1. Identification of novel compounds that modulate or inhibit our prime cancer cell targets by screening of chemical libraries
2. Elucidation of the mechanism of action of hit compounds, i.e. their molecular targets, specificity in vitro and in vivo, and possible off-target effects.
3. Validation of identified compounds in clinical samples by performing extensive multidimensional computational biology-guided analysis of clinical samples and linking this information to the response to our hit compounds, detailed clinical information and long-term follow up.
4. Evaluation and validation of the effect of lead compounds on tumor cells and tumor stroma in vivo using animal models already established by ACT! PIs, as well as newly developed primary tumor cells-based xenograft models.
5. Establishment of methodology for molecular diagnostics and development of individually tailored therapy by introducing the HTP imaging technology for large-scale screening of sensitivity of patient samples to conventional and experimental anticancer drugs and their combinations in order to guide clinical decision making and individualized therapy in the clinic.
6. Pre-clinical development of selected candidate drugs and initiation of first-in-man, Phase I and Phase II clinical trials.
