The research interests of Alexey A. Leontovich, Ph.D., focus on two aspects of cancer biology.
The first is oscillatory patterns in the immune system of cancer patients and identification of optimum time (the state of the immune system) for chemotherapy administration. Dr. Leontovich is a member of the Melanoma Study Group of the Mayo Clinic Cancer Center and studies primarily time-dependent patterns in the immune system of melanoma patients. The concept, methodology and algorithms for identification of optimum time of treatment will be extended to other types of cancer once they are validated in melanoma patients.
The second is transcriptional reprogramming in the course of metastatic progression in breast cancer. Dr. Leontovich has long-standing collaboration with clinicians and basic scientists at Mayo Clinic who, as a team, study different aspects of this problem.
- Prediction of immunologic state of cancer patients, favorable for chemotherapy administration. In collaboration with Svetomir N. Markovic, M.D., Ph.D., in the Melanoma Study Group, Dr. Leontovich studies time-dependent concentration patterns of cytokines and immune-competent cells and the relation of these concentrations on the day of treatment with clinical outcome. The goal is to develop an algorithm that, based on immunologic measurements, can predict a day that is most favorable for chemotherapy administration.
- Transcriptional reprogramming during metastatic progression in breast cancer. In collaboration with clinical investigators and basic scientists, Dr. Leontovich characterizes transcriptional switches in metastasis, initiating cells responsible for successful metastatic seeding and growing in the new host environment. Using tumor xenografts in animal model, immunostaining, gene microarray technology and bioinformatics analysis, this research group elucidates key transcriptional regulators of metastatic progression.
- Molecular mechanisms of metabolic memory in diabetes. Dr. Leontovich studies heritable transmissible aberrations in DNA methylation and gene expression changes caused by hyperglycemia in a model organism — zebrafish. This research project is being done in collaboration with Michael P. Sarras Jr., Ph.D., and colleagues at the Rosalind Franklin University of Medicine and Science.
Significance to patient care
Synchronizing conventional chemotherapy delivery with individualized immune kinetics appears to significantly improve progression-free survival in melanoma patients. This finding raises the possibility that cancer drug therapy delivered in synchrony with endogenous immune kinetics may improve clinical outcomes of existing cancer drugs in different types of cancer.
Understanding molecular mechanisms of transcriptional reprogramming during metastatic progression will allow scientists to develop new pharmaceuticals that can block or slow down the development of metastases.