2022 Fiscal Year Annual Research Report
Mathematical Modeling of Drug Resistance Evolution and The Optimal Treatment Strategy in EGFR Mutated Lung Cancer
| Project/Area Number |
22J10101
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| Allocation Type | Single-year Grants |
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Yu Qian 東京大学, 大学院新領域創成科学研究科, 特別研究員(DC2)
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| Project Period (FY) |
2022-04-22 – 2024-03-31
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| Keywords | EGFR / mathematical modeling / T790M / EGFR-TKIs |
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| Outline of Annual Research Achievements |
In 2022, I followed my research plan and made some progress. My research is about using a mathematical model to simulate tumor progression in different therapies and predict the optimal treatment strategies for patients. Firstly, in order to get the data for model simulation, I established two types of EGFR mutation cells and co-culture them. In this experiment, I observed that drug-sensitive cells survived in drugs even with only 10% existence of drug-resistant cells. Also, this kind of co-culture response is different from different drugs, we may explore the mechanism of this phenomenon in the future. Secondly, I simulated the time course of tumor progression in different therapy strategies and analyzed the influence effect of drug-resistance cells on drug-sensitive cells through computational simulation. In this theoretical analysis, results indicated that although all-drug-resistant cells are expected to be the strongest support for helping all-drug-sensitive cells to survive because they resistant all therapy drugs, but actually it does not. Out of expectation, secondary mutation cells, which are one-drug-resistant cells, help the survivor of all-drug-sensitive cells more than all-drug-resistant cells. This might because the growth of all-drug-resistant cells is slower compared with one-drug-resistant cells in the corresponding drugs, which means all-drug-resistant cells may spend more “effort” in “self-survivor”. We would like to research its mechanism in the future, too.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
My plan for 2022 is to establish cell lines and co-culture drug-sensitive and drug-resistant cells to know how much the growth rate will change compared with mono-culture. In 2022, I established the needed cell lines, which are EGFR-L858R/C797S mutation and EGFR-L858R/T790M/C797S mutation cells. Then, I co-cultured drug-sensitive cells and drug-resistant cells to measure the growth rate changes compared with mono-culture. Based on the experiment results, I realized the growth rate may be variable with the proportion change of different tumor cells which is impossible being detected by current technology. Therefore, I simulated tumor progression with changeable growth rate with tumor proportions and did some research that in the plan of 2023.
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| Strategy for Future Research Activity |
In 2023, I am going to do parameter analysis and figure out the optimal therapy strategies theoretically according to different initial information, such as mutation types, resistant cell proportions and different EGFR-TKIs. I would like to analyze how tumor progression will change with different parameters, because parameters can reflect the change of conditions. For example, the drug potency, cell-cell interactions, and how the number of tumor cells responds to these changes. Parameter analysis can offer many valuable information about tumor progression in different therapies and may provide prospective guidance for clinical application. Finally, the results might be summarized into an interactive screening system for suggesting the optimal therapy strategies theoretically.
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