Massively parallel cancer evolution simulation to elucidate mechanisms of intratumor heterogeneity generation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12214
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Niida Atsushi 東京大学, 医科学研究所, 講師 (00772493)
• Co-Investigator(Kenkyū-buntansha): 岩嵜 航 東北大学, 生命科学研究科, 助教 (30838959)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: がん / シミュレーション / 進化

Outline of Final Research Achievements

In this study, we constructed a simulation model that describes the various evolutionary patterns of cancer in a unified way, and explored the mechanism of intratumor heterogeneity (ITH) generation in cancer through massively parallel simulations and parameter sensitivity analysis using a supercomputer. As a result, several interesting findings were extracted. For example, we found not only that a high mutation rate leads to the formation of extensive ITH by neutral evolution, but also that the cancer stem cell hierarchy contributes to the formation of the neutral ITH by increasing the apparent mutation rate. It has also become clear that the evolutionary shifts observed during colorectal tumorigenesis may be caused by dramatic evolutionary events that occur in a short period of time and result in significant fitness gains in one or a few cells.

Free Research Field

計算生物学

Academic Significance and Societal Importance of the Research Achievements

がんは細胞のゲノムに変異が蓄積し増殖能力、悪性度の高い細胞が進化的に選択された結果生じる進化の病気だと捉えることができる。がんはその進化能力の高さゆえ、治療によって変わった環境にも適応し容易に治療抵抗性を獲得してしまうので、がんの進化原理の理解は治療戦略を練る上でも重要な問題である。本研究はがんの進化を理解する上での数理的な基盤を提供することで、今後のがんの治療抵抗性の理解及びそれに基づいた治療戦略の開発に資すると期待される。