建模获得性耐药性对癌症治疗结果的影响
M A Masud1, Jae-Young Kim2, Eunjung Kim1
1Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea.
Computers in biology and medicine
|June 5, 2023
概括
适应疗法 (AT) 通过利用细胞竞争,有效地管理瘤. 然而,受突变率和表型变化的影响,获得的耐药性可能会改变AT疗效,需要量身定制的治疗策略.
科学领域:
- 计算生物学是一种计算生物学.
- 癌症研究 癌症研究
- 进化的动力学.
背景情况:
- 适应疗法 (AT) 是一种基于进化的策略,利用细胞之间的竞争.
- 癌细胞中获得的耐药性可以改变瘤的竞争力,并影响AT结果.
- 了解抵抗机制对于优化癌症治疗至关重要.
研究的目的:
- 在获得癌细胞耐药性的情况下,研究适应性治疗 (AT) 的疗效.
- 模拟空间瘤生长,并分析不同抵抗机制对AT结果的影响.
- 开发一种用于量化耐药细胞空间分布的新方法.
主要方法:
- 开发了一个基于代理的空间瘤生长模型.
- 包括三种类型的获得性耐药性:随机突变,可逆的表型变化和不可逆的表型变化.
- 提出并使用采样里普利的K函数 (SRKF) 来量化阻力分布.
主要成果:
- 耐药性的新兴空间分布显著影响了在AT和连续疗法 (CT) 下进展的时间.
- 高突变率可以导致在AT下比CT更快的进展,这是由于抗性细胞凝聚.
- 药物诱导的耐药性加速瘤的进展,需要积极的CT,但最佳的AT剂量可以延迟复发.
结论:
- 不同的抗性机制极大地影响了抗性分布,从而决定了AT疗效.
- 耐药性的空间分布是预测治疗结果的关键因素.
- 在AT下最佳的剂量策略可以抑制抗性并延迟瘤复发.
相关概念视频
Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Cancer Survival Analysis
402
Cancer survival analysis focuses on quantifying and interpreting the time from a key starting point, such as diagnosis or the initiation of treatment, to a specific endpoint, such as remission or death. This analysis provides critical insights into treatment effectiveness and factors that influence patient outcomes, helping to shape clinical decisions and guide prognostic evaluations. A cornerstone of oncology research, survival analysis tackles the challenges of skewed, non-normally...
402
Adaptive Mechanisms in Cancer Cells
5.8K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
Cancer Therapies
7.8K
Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.8K


