Exploiting The Heterogeneous Composition Of Tumor Tissue And The Altered Metabolism Of Tumor Cells For Cancer Therapy Design
利用肿瘤组织的异质组成和肿瘤细胞代谢的改变进行癌症治疗设计
基本信息
- 批准号:1404314
- 负责人:
- 金额:$ 47.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-08-01 至 2018-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Title: Exploiting the heterogeneous composition of tumor tissue and the altered metabolism of tumor cells for cancer therapy designThe number of cells in an adult multicellular organism such as a human being is under very tight control and, under normal circumstances; there is some kind of a balance between new cell production and cell death. Roughly speaking, cancer results when there is excessive cell division or reduced cell death due to some malfunctioning in the cell number control system. What makes cancer therapy so difficult is that this malfunctioning can happen in many different ways and at many different locations and would, therefore, require different tailored treatments. Furthermore, cancer tissue is usually heterogeneous in the sense that it is a mixture of cells with different malfunctions. As a result, directing treatment at one type of malfunctioning cells may lead to the dominant emergence of other types of malfunctioning cells, manifesting itself in the phenomenon of acquired drug resistance usually observed in cancer therapy. Thus, to achieve better therapeutic outcome, the dominant cell subpopulation needs to be identified so that the therapy can be targeted towards it. The first goal of this project is to experimentally demonstrate the feasibility of such an approach using a heterogeneous mixture of cancer cell lines. The second goal of this project is to exploit metabolic alteration in cancer cells to design therapies that differentially target cancer cells. More specifically, the project seeks to experimentally validate via cancer cell lines the benefits of including the anti-diabetic (metabolism targeting) drug Metformin as part of a combination cocktail therapy for cancer. Since both the goals are directed towards improving cancer treatment, the potential societal benefits of this project could be enormous. In addition, the project will be carried out at the newly formed Center for Bioinformatics and Genomic Systems Engineering (CBGSE) at Texas A & M University, where widespread dissemination of the research results, imparting truly interdisciplinary hands-on education to graduate students, and beneficially targeting minorities and minority institutions, are top priorities.Cancer is an umbrella term for a large number of diseases that are associated with loss of cell-cycle control, leading to uncontrolled cell proliferation and/or reduced apoptosis (programmed cell death). This loss of cell-cycle control usually results from different malfunction(s) in the cellular signaling pathways. Since cancer tissue is usually heterogeneous, it is appropriate to first identify the dominant subpopulation and then accordingly tailor the targeted treatment, hopefully achieving a better therapeutic outcome. The first goal of this project is to utilize such an approach, developed using hierarchical Bayesian methods, and experimentally validate it using a mixture of cancer cell lines, harboring known mutations. To introduce the second goal, we note that the traditional approach to cancer therapy is to induce cancer cell death by using therapeutic drugs, radiation, etc. Most of these treatments are toxic to normal cells and carry significant side effects. On the other hand, cancer cells are known to be addicted to glucose while normal adult cells are not. This brings up the natural question as to whether the preferential killing of cancer cells could be achieved by targeting the supply of glucose. Indeed, epidemiological studies have shown that the commonly used anti-diabetic drug Metformin has beneficial effects in preventing or slowing the onset of breast and certain other cancers. Motivated by this, the second goal of this project is to experimentally study the role of Metformin in cancer therapy when used as part of a combination therapy design. Since most chemotherapeutic drugs have toxic side effects while Metformin does not, including the latter as part of a combination therapy for cancer certainly has the potential to enhance the quality of life for cancer patients.
职务名称:利用肿瘤组织的异质性组成和肿瘤细胞代谢的改变用于癌症治疗设计在成人多细胞生物体(如人类)中的细胞数量处于非常严格的控制之下,并且在正常情况下,在新细胞产生和细胞死亡之间存在某种平衡。粗略地说,当细胞数量控制系统出现故障而导致细胞过度分裂或细胞死亡减少时,就会产生癌症。癌症治疗之所以如此困难,是因为这种故障可能以许多不同的方式发生在许多不同的位置,因此需要不同的定制治疗。此外,癌组织通常是异质的,因为它是具有不同功能障碍的细胞的混合物。因此,针对一种类型的故障细胞进行治疗可能导致其他类型的故障细胞的主导出现,表现为通常在癌症治疗中观察到的获得性耐药性现象。因此,为了达到更好的治疗效果,需要确定占主导地位的细胞亚群,以便治疗可以针对它。该项目的第一个目标是实验证明这种方法的可行性,使用异质混合物的癌细胞系。该项目的第二个目标是利用癌细胞中的代谢改变来设计差异靶向癌细胞的疗法。更具体地说,该项目旨在通过癌细胞系实验验证将抗糖尿病(代谢靶向)药物Metabolic作为癌症联合鸡尾酒疗法的一部分的益处。由于这两个目标都是为了改善癌症治疗,该项目的潜在社会效益可能是巨大的。此外,该项目还将在新成立的德克萨斯A M大学生物信息学和基因组系统工程中心(CBGSE)进行,该中心的首要任务是广泛传播研究成果,向研究生提供真正的跨学科实践教育,并有益地针对少数民族和少数民族机构。癌症是一个总括术语,涉及大量与细胞周期失控有关的疾病,导致细胞增殖失控和/或细胞凋亡减少(程序性细胞死亡)。这种细胞周期控制的丧失通常是由细胞信号传导途径中的不同故障引起的。由于癌症组织通常是异质性的,因此首先确定占主导地位的亚群,然后相应地调整靶向治疗,有望实现更好的治疗结果。该项目的第一个目标是利用这种方法,使用分层贝叶斯方法开发,并使用含有已知突变的癌细胞系的混合物进行实验验证。为了介绍第二个目标,我们注意到,传统的癌症治疗方法是通过使用治疗药物,辐射等诱导癌细胞死亡,这些治疗方法大多对正常细胞有毒,并具有显着的副作用。另一方面,已知癌细胞对葡萄糖上瘾,而正常的成年细胞则不会。这就提出了一个自然的问题,即是否可以通过靶向葡萄糖的供应来优先杀死癌细胞。事实上,流行病学研究表明,常用的抗糖尿病药物美托洛尔在预防或减缓乳腺癌和某些其他癌症的发病方面具有有益的效果。受此启发,该项目的第二个目标是实验研究Metaldehyde作为联合治疗设计的一部分在癌症治疗中的作用。由于大多数化疗药物都有毒副作用,而美托洛尔没有毒副作用,因此将后者作为癌症联合治疗的一部分肯定有可能提高癌症患者的生活质量。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Aniruddha Datta其他文献
Robust and Optimal PID Controller Design
- DOI:
10.1016/s1474-6670(17)42581-x - 发表时间:
1997-06-01 - 期刊:
- 影响因子:
- 作者:
Ming-tzu Ho;Aniruddha Datta;L.H. Keel;S.P. Bhattacharyya - 通讯作者:
S.P. Bhattacharyya
In Vitro Flowering and High Xanthotoxin in Ammi majus L.
- DOI:
10.1007/bf03262956 - 发表时间:
2012-12-30 - 期刊:
- 影响因子:1.500
- 作者:
Madhumati Purohit;Deepshikha Pande;Aniruddha Datta;Prem S. Srivastava - 通讯作者:
Prem S. Srivastava
An addition to the endemic Indian radiation of Eutropis: Phylogenetic position of Eutropis dissimilis Hallowell (Squamata: Scincidae).
印度地方性辐射Eutropis的补充:Eutropis dissimilis Hallowell(有鳞目:Scincidae)的系统发育位置。
- DOI:
10.11646/zootaxa.4027.1.9 - 发表时间:
2015 - 期刊:
- 影响因子:0.9
- 作者:
Aniruddha Datta;V. Deepak;Chinta Sidharthan;A. J. Barley;K. Karanth - 通讯作者:
K. Karanth
Phylogeny of endemic skinks of the genus Lygosoma (Squamata: Scincidae) from India suggests an in situ radiation
印度石龙子属(Squamata:Scincidae)地方性石龙子的系统发育表明存在原位辐射
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
Aniruddha Datta;Mewa Singh;K. Karanth - 通讯作者:
K. Karanth
Anti-tumor effects of cryptotanshinone (Csub19/subHsub20/subOsub3/sub) in human osteosarcoma cell lines
隐丹参酮(C₁₉H₂₀O₃)在人骨肉瘤细胞系中的抗肿瘤作用
- DOI:
10.1016/j.biopha.2022.112993 - 发表时间:
2022-06-01 - 期刊:
- 影响因子:7.500
- 作者:
Haswanth Vundavilli;Aniruddha Datta;Chao Sima;Jianping Hua;Rosana Lopes;Michael Bittner;Tasha Miller;Heather M. Wilson-Robles - 通讯作者:
Heather M. Wilson-Robles
Aniruddha Datta的其他文献
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{{ truncateString('Aniruddha Datta', 18)}}的其他基金
I-Corps: Model-driven precision oncology for cancer therapy design
I-Corps:用于癌症治疗设计的模型驱动的精准肿瘤学
- 批准号:
2136215 - 财政年份:2021
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Cancer Therapeutics through Theory and Experiment: From Cell Lines to Canine Tumors Grown on the Back of Mice
通过理论和实验进行癌症治疗:从细胞系到小鼠背部生长的犬肿瘤
- 批准号:
1917166 - 财政年份:2019
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Identification of Drug Targets and Their Validation in Cancer Therapy Design
癌症治疗设计中药物靶标的识别及其验证
- 批准号:
1609236 - 财政年份:2016
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Student Travel Award Support for GENSIPS'13
对 GENSIPS13 的学生旅行奖支持
- 批准号:
1342663 - 财政年份:2013
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Cancer Therapy Design Based on Pathway Information
基于通路信息的癌症治疗设计
- 批准号:
1068628 - 财政年份:2011
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Modeling and Control in Cancer Genomics
癌症基因组学的建模和控制
- 批准号:
0701531 - 财政年份:2007
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Controller Synthesis Subject to Structure and Order Constraints
受结构和阶次约束的控制器综合
- 批准号:
9903488 - 财政年份:1999
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Robust Adaptive Control Based on Kharitonov Theory and Its Extensions
基于Kharitonov理论及其扩展的鲁棒自适应控制
- 批准号:
9417004 - 财政年份:1995
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
Robustness Quantification and Performance Improvement in Adaptive Control Systems
自适应控制系统的鲁棒性量化和性能改进
- 批准号:
9210726 - 财政年份:1992
- 资助金额:
$ 47.77万 - 项目类别:
Standard Grant
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