My research works aim to develop combined mathematical, experimental and clinical methodologies to personalize anticancer treatments based on the molecular physiology of the host and of the tumour.
Indeed, drug toxicity is ultimately determined by the gene and protein networks involved in drug pharmacokinetics-pharmacodynamics (PK-PD), which constitutes a reliable basis for treatment optimization. The molecular and dynamical understanding of drug PK-PD is thus critical to integrate tumour mutations and patient’s sex and genetic background in treatment decision. However, this complex physiology and its temporal organization are unlikely to be completely assessed in individual cancer patients due to the invasive and potentially unethical nature of the clinical measurements that would be required. We thus develop multi-scale systems medicine approaches integrating experimental results in cell culture, rodent and clinical investigations to compute sex-specific and ultimately patient-specific treatment regimens.
Current projects include the individualization of anticancer chronotherapy for metastatic colorectal malignancies focusing on the combination of the anticancer drug irinotecan, oxalipaltin and 5-fluorouracil to targeted therapies, in collaboration with Inserm team U935 (Hôpital Paul Brousse, Villejuif , Paris). Ongoing researches also aim to individualize temozolomide-based combination chemotherapies against glioblastomas, in collaboration with the Experimental Neuro-oncology team at the Institut du Cerveau et de la Moelle Epinière (Hôpital La Pitié Salpétrière, Paris).
S. Dulong, A. Ballesta, A. Okyar, F. Lévi : Identification of circadian determinants of cancer chronotherapy through in vitro chronopharmacology and mathematical modeling, Molecular Cancer Therapeutics, 2015, 14(9):2154-64.
A. Ballesta, Q. Zhou, X. Zhang, H. Lv, JM. Gallo: A multi-scale approach to develop cell type-specific pharmacokinetic/pharmacodynamic models: intracellular brain and brain tumor disposition of temozolomide, CPT: pharmacometrics and systems pharmacology, 2014, 3, e112.
A. Ballesta, M. Doumic-Jauffret, J. Lopez, P. Gonzalo, G. Gillet: Modeling Src control on the mitochondrial pathway of apoptosis, implications for cancer therapeutics, PLoS Computational Biology, 2013 Apr; 9(4):e1003011
A. Ballesta, S. Dulong, A. Okyar, C. Abbara, B. Cohen, J. Clairambault , F. Levi: A combined biological and mathematical approach for studying the circadian control of the anticancer drug Irinotecan Pharmacokinetics-Pharmacodynamics at a molecular level, PLoS Computational Biology, 2011 Sep; 7(9):e1002143.