(1) Screening of compounds at different stages of development using innovative biological platforms.
(2) Singular projects of preclinical drug development based on the business strategy of each Company.
Our biological platforms are used with drugs under development to study their efficacy in different tumor stages or the sinergy between two or more drugs.
Surgical samples serve as starting material to isolate different tumor cell populations, including cancer stem (or initiating) cells and tumor parenchymal cells.
The major advantages of cancer stem cells reside in their genetic stability in long-term culture and their capacity to generate a phenocopy of the original tumor in xenografted animals.
On the other hand, tumor parenchymal cells provide a ready-to-use cellular model and can also be maintained and expanded for several weeks.
Tumor cells are injected into zebrafish and chicken embryos, and then treated with drugs. Following treatment, embryos are studied to detect the viability of tumor cells or other biological features such as proliferation capacity, invasiveness and differentiation. Additionally, the acute (death of the organism) and organ-specific (defects in organ development) toxicity to the embryos is also analyzed.
The main features of these models are rapidity, low-cost and versatility. They are well suited to approach different aspects of the tumor biology, including proliferation, cell survival, migration, differentiation and angiogenesis, and to test the toxicity (acute and organ-specific) of new anti-tumor compounds.
(a) Zebrafish embryos. The zebrafish is a vertebrate and shares many developmental and genetic similarities with humans. Most human genes studied so far have orthologs in the zebrafish. Thanks to their transparency, zebrafish embryos and early larvae facilitate analysis of xenografted tumor cells because they can be tracked at the level of the individual cell in the living animal. Zebrafish-based assays are increasingly utilized by industry to screen for drug/toxicant effects.
(b) Chicken embryos. Within 2 to 3 days after fertilization, embryos become organisms with a beating heart and a complex nervous system. At these early stages, embryos are big enough to allow micromanipulation and injection of tumor cells in defined structures. The chicken embryo model has been an important tool to study tumor growth, metastasis and angiogenesis, and several companies now offer this model as legal animal replacement for toxicological studies.
