癌细胞的阿基里斯脚跟:设计抗癌药物组合的考虑因素
Valid Gahramanov1,2, Frederick S Vizeacoumar3, Alain Morejon Morales3,4
1Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
International journal of molecular sciences
|January 8, 2025
概括
识别癌细胞的"阿基里斯高跟"包括分析基因路径. 针对这些弱点,如蛋白酶或RNA合成,使瘤对各种抗癌药物敏感,改善组合疗法.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 使用短发针RNA (shRNA) 和集群定期间隔的短Palindromic重复 (CRISPR) 的功能丧失屏幕识别影响癌症药物反应的基因.
- 基因组丰富分析 (GSEA) 和连接地图 (CMAP) 是用于分析大规模查数据的强大生物信息学工具.
研究的目的:
- 确定代表癌细胞"弱点"的核心生物通路,使其易受多种抗癌药物的侵害.
- 研究是否抑制这些已识别的"弱点"可以使癌细胞对更广泛的治疗药物的敏感性.
主要方法:
- 使用GSEA和CMAP对多个已发表的shRNA查的综合分析.
- 确定调节对各种抗癌药物反应的核心途径.
- 使用FDA批准的蛋白酶体,RNA合成和Akt-mTOR通路的抑制剂进行实验验证,以评估药物协同作用.
主要成果:
- 一组核心途径,包括蛋白酶体,蛋白质合成,RNA剪接,RNA合成,细胞循环,Akt-mTOR和紧密结合途径,被确定为"弱点".
- 针对这些"弱点"的抑制剂与其他标的抑制剂相比,与更多样化的药物配合表现出协同作用.
- 定量评估证实,针对这些核心途径可以提高对各种抗癌药物的敏感性.
结论:
- 已识别的"弱点"途径对癌细胞存活至关重要,并且代表了组合疗法的有希望的目标.
- 这些核心途径的抑制剂应优先考虑作为开发协同作用的抗癌药物组合的候选药物.
- 针对这些途径提供了一种合理的策略,以克服耐药性并提高癌症治疗的疗效.
更多相关视频
07:40A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
4.1K
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017
10.9K
相关概念视频
02:50Combination Therapies and Personalized Medicine
4.8K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.8K
02:57Targeted Cancer Therapies
7.4K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.4K
02:56Treatment Resistant Cancers
3.2K
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...
3.2K
02:49Cancer Therapies
7.5K
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...
7.5K
02:53Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K
02:40Cancer Stem Cells and Tumor Maintenance
4.7K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.7K