糖核酸クリアランスの障害は,がん細胞の治療的脆弱性です
Mihir B Doshi1, Namgyu Lee1,2, Tenzin Tseyang3
1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nature
|October 25, 2023
まとめ
癌細胞は 糖核酸経路の脆弱性を利用します 酵素UXS1は,UGDHが高いがん細胞における過剰なUDPGAの解毒に不可欠であり,ターゲットを絞った治療戦略を提供します.
科学分野:
- 生物化学
- 癌 代謝
- 分子生物学
背景:
- ターゲットを絞った治療には,がん特有の代謝依存性の特定が不可欠です.
- 糖核酸生物合成経路は,がんの進行における役割としてますます認識されています.
研究 の 目的:
- 癌細胞が利用できる 糖核酸代謝の 治療的脆弱性を特定する
- がん細胞における UXS1 酵素の条件付き本質性を調査する.
主な方法:
- 条件として必須の代謝酵素の体系的な検査
- UDP-グルキュロン酸 (UDPGA) の解毒経路の分析
- UGDHとUXS1発現レベルとの関係を調査する.
主要な成果:
- UXS1は,UGDH発現が高いがん細胞において条件的に必須である.
- UXS1は,Golgi機能と細胞シグナル伝達を妨害するUDPGAの毒性蓄積を防ぐ.
- 肺アデノカルシノーマなどのがんでは,UGDHの発現が上昇し,その後のUXS1への依存が観察されています.
結論:
- 高いUGDHを持つ癌細胞は,UDPGAの解毒のためにUXS1に選択的に依存している.
- この依存性は,UGDHが高い腫瘍における潜在的な治療上の弱点を示しています.
- UXS1-UGDH軸を標的にすることは,正常な細胞に限られた影響を及ぼすがん治療の有望な戦略です.
関連する概念動画
Treatment Resistant Cancers
3.3K
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...
3.3K
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
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Targeted Cancer Therapies
7.7K
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...
7.7K
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Combination Therapies and Personalized Medicine
4.9K
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...
4.9K


