Mathematical Modeling to Study KRAS Mutant-Specific Responses to Pathway Inhibition.
Mathematical Modeling to Study KRAS Mutant-Specific Responses to Pathway Inhibition.
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DOI：
10.1007/978-1-0716-1190-6_19
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发表时间：
2021
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影响因子：
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通讯作者：
Stites EC
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作者：
Stites EC
本章将描述数学建模如何允许通过计算实验来研究RAS途径。所使用的数学模型模拟调节RAS信号的生化反应。这种类型的模型结合了反应机制的知识，包括测量的定量参数，这些参数表征了野生型和突变的RAS蛋白的这些反应。作为一个说明性的例子，本章重点介绍建模如何提供新的见解，帮助解决一个困扰RAS社区近十年的问题：为什么带有KRAS G13D突变的结直肠癌，而不是其他常见的KRAS突变，可以受益于EGFR抑制。所描述的方法包括计算剂量反应实验和“计算嵌合”RAS突变体的使用。
This chapter will describe how mathematical modeling allows the RAS pathway to be studied with computational experiments. The mathematical model utilized simulates the biochemical reactions that regulate RAS signaling. This type of model incorporates knowledge of reaction mechanisms, including measured quantitative parameters that characterize these reactions for both wild-type and mutant RAS proteins. For an illustrative example, this chapter focuses on how modeling provided new insights that helped solve a problem that challenged the RAS community for nearly a decade: why do colorectal cancers with the KRAS G13D mutation, but not the other common KRAS mutations, benefit from EGFR inhibition. The methods described include computational dose response experiments and the use of “computational chimeric” RAS mutants.