PTPRK-RSPO3の結腸腫瘍を標的とすることは,幹細胞の分化と機能の喪失を促進する

Elaine E Storm¹, Steffen Durinck², Felipe de Sousa e Melo¹

¹Molecular Oncology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.

Nature

|December 25, 2015

まとめ

PTPRK- RSPO3融合による大腸腫瘍におけるRSPO3の標的化は,成長を阻害し,分化を促進する. このアプローチは癌の幹細胞を標的とし結腸直腸がんの新たな治療法となる可能性があります

科学分野:

腫瘍学
遺伝学
分子生物学

背景:

結腸直腸がん (CRC) は,多くの治療需要が満たされていない重大な健康問題です.
ゲノム研究は,標的治療の開発のためのCRCドライバーを特定することを目的としています.
R- スポンジンの遺伝子の転位は以前,大腸直腸腫瘍のサブセットで発見されました.

研究の目的:

PTPRK- RSPO3融合を宿す大腸腫瘍におけるRSPO3を標的とした治療の可能性を調査する.
PTPRK-RSPO3-駆動の結腸直腸腫瘍の成長における腸の幹細胞の役割を調査する.

主な方法:

PTPRK-RSPO3融合陽性の大腸内腫瘍からのヒト腫瘍異種移植を用いた.
標的型抗RSPO3療法を行いました.
敏感な経路を特定するために遺伝子発現分析を行った.
腫瘍の反応を評価する機能検査を実施した.

主要な成果:

PTPRK- RSPO3融合陽性の異種移植において,RSPO3を標的とした治療は,腫瘍の成長を有意に抑制した.
RSPO3抑制は腫瘍細胞の分化を促進した.
腸の幹細胞と関連した遺伝子は,抗RSPO3治療に非常に敏感でした.

結論:

RSPO3は,PTPRK-RSPO3融合によって特徴づけられる大腸内腫瘍のサブセットにおける重要な原動力である.
結腸直腸腫瘍の成長は幹細胞によって引き起こされます
PTPRK-RSPO3融合陽性の結腸直腸がんの治療には,がん幹細胞の特性をターゲットにすることが有望な戦略である.

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