Buenos Aires
Breast Cancer
Symposium

BA-BCS 2024

September 3 – 6, 2024

IFIBYNE Auditorium, FCEN-UBA

Poster No. 65

Design of a platform to rank chemotherapeutic drugs with a multidimensional approach

Florencia Hernandez1, Lilen Ivonne Caimi1, Ginette Moyano1, Vanesa Gottifredi1, Nicolás Luis Calzetta1

1.Instituto de Investigaciones Bioquímicas de Buenos Aires .

Presenting Autor:
Hernandez, Florencia

Fundación Instituto Leloir

Cancer is the leading cause of death worldwide. As a result, over 100 chemotherapy drugs have been approved in an attempt to cure or control the disease, while there are still thousands more candidates undergoing clinical trials. One of the challenges currently faced by cancer researchers is the need to rank these drugs based on their safety and efficacy, as the only available variables. We propose to design, generate and test a novel platform that compares drugs using a multidimensional pipeline. Such an approach may provide substantial improvement the traditional unidimensional approach based on cancer cell killing potential. By applying automated image capture by fluorescence microscopy, our platform is designed to simultaneous- and comparatively evaluate cytotoxic capacity, impact on the cell cycle profile, incorporation of genomic instability features and levels of DNA damage accumulation. A drug that (1) has high cytotoxic efficacy (2) causes massive DNA damage, and (3) causes cell death without leading to cell cycle arrest will be categorized as best candidates by our platform. We have succeeded in fine-tuning this platform using the DNA dye, DAPI, and the antibody against histone γH2AX as a DNA damage marker. Furthermore, we also adapted our setting to perform a novel imaging analysis called QIBC (quantitative imaging based cytometry), which reveals the stage of the cell cycle at which a chemotherapeutic drug induces DNA damage. Such settings will therefore produce information related to the mode of action of the drug candidates and use that information to rank them. We initiated the development of this platform using the osteosarcoma cell line, U2OS, exposed to a checkpoint kinase 1 inhibitor (CHK1i) with are experimental setting that we have used extensively in the past. The pipeline will then be use to compare a list of drugs that is currently being evaluated in clinical trials in order to test the ranking power of our platform.

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