循環 がん 細胞 は 異なった プログラム を 持つ 系統 から 生じる
Yaara Oren1,2, Michael Tsabar1,3,4, Michael S Cuoco1
1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature
|August 12, 2021
まとめ
癌細胞は薬剤耐性の状態に入り 薬剤治療に耐えることができます 新しい研究によると 特定の代謝と遺伝子発現プログラムにより 持続性のある細胞が増殖し 癌の再発を防ぐ新しい治療標的を 提供しています
科学分野:
- 癌 生物学
- 遺伝学
- メタボリズム
背景:
- 非遺伝的メカニズムは がん治療の失敗の重要な要因としてますます認識されています
- 癌細胞は薬剤耐性の状態に入り,薬剤の継続的な曝露下で増殖を維持するサブセットがあります.
- 薬剤にさらされた持続細胞の増殖能力を可能にするメカニズムは,ほとんど不明である.
研究 の 目的:
- 癌細胞の増殖能力の根底にある非遺伝的メカニズムを調査する.
- サイクリングに関連した異なる系統と転写/代謝プログラムを特定する.
- 薬物耐性菌群の 治療上の脆弱性を調査する
主な方法:
- クローン トレーシングと状態モニタリングを同時に行うためのウォーターメロンのレンチウイルスバーコードシステムの開発.
- 細胞のクローン起源,増殖,転写状態の分析
- 細胞循環における酸化ストレスと代謝再プログラミングの役割の調査
主要な成果:
- 循環性および非循環性パーシスターは,独特の転写および代謝プロファイルを持つ異なる細胞系統から発生します.
- 抗酸化プログラムと脂肪酸の酸化の上昇は,がんの種類にわたる持続的な増殖能力と関連しています.
- 酸化ストレスや代謝再プログラムによる干渉は,サイクリングの割合に影響を及ぼします.
- 標的治療で治療されたヒト腫瘍の最小残留疾患では,持続性細胞プログラムが観察されています.
結論:
- ウォーターメロンのシステムは 薬剤の圧力下で 稀な,増殖性の持続的な系統を 効果的に特定します
- 代謝の再プログラムと抗酸化防御は 癌の細胞増殖に不可欠です
- これらの特定された脆弱性をターゲットにすることで 癌の再発と疾患の進行を防ぐ戦略が提供されるかもしれません
関連する概念動画
02:40Cancer Stem Cells and Tumor Maintenance
5.1K
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...
5.1K
02:21Cancers Originate from Somatic Mutations in a Single Cell
13.3K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
13.3K
02:12What is Cancer?
12.2K
Cells and tissues must meticulously coordinate their activities for the normal functioning of the human body. Therefore, they exhibit socially responsible behavior - resting, growing, dividing, differentiating, or dying - for the organism’s benefit. Cancer arises when cells divide uncontrollably and invade other tissues or organs.
Although people have known about cancer for centuries, it was only in 1761 that Giovanni Morgagni of Padua performed a detailed autopsy of...
Although people have known about cancer for centuries, it was only in 1761 that Giovanni Morgagni of Padua performed a detailed autopsy of...
12.2K
02:53Adaptive Mechanisms in Cancer Cells
6.0K
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,...
6.0K
02:56Treatment Resistant Cancers
3.5K
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...
3.5K
01:16Cell Lines
9.1K
A cell line is a population of cells grown in vitro that can be subcultured over several generations. Normal cells cease to divide after a certain number of cell divisions, a process known as replicative senescence. This number, called the Hayflick limit, was conceptualized by Leonard Hayflick in 1961 when he observed that fetal cells grown in culture could only divide 40-60 times. This limit is due to the shortening of the telomeres during each round of cell division, preventing cell division...
9.1K