JP2017504623A - ヘテロ接合性の喪失を示す乳癌または卵巣癌の患者を治療するためのparp阻害剤の使用 - Google Patents
ヘテロ接合性の喪失を示す乳癌または卵巣癌の患者を治療するためのparp阻害剤の使用 Download PDFInfo
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Abstract
Description
LOHの存在を基準としてDNA損傷を示した乳癌及び卵巣癌の患者を、PARP阻害剤、特にルカパリブで治療することは本発明の主な目的である。乳房腫瘍または卵巣腫瘍におけるLOHの存在により、医師の治療選択が助けられる。
実施例1
ルカパリブ感受性乳癌細胞はゲノムLOHを示す。
ルカパリブ感受性細胞
統計
結果
実施例2−プラチナベースの治療からのゲノムLOH有効性を示す腫瘍を有する卵巣癌患者
高悪性度漿液性卵巣腫瘍
LOH分析
統計
結果
実施例3−ルカパリブ治療からのゲノムLOH有効性を示す腫瘍を有する卵巣癌患者
患者由来の卵巣腫瘍の次世代塩基配列決定
LOH分析
結果
患者由来の高悪性度卵巣腫瘍の次世代塩基配列決定
LOH分析
方程式で表すと:
LOHを持つゲノムの% =100*Σ(非除外LOH領域の長さ)/(SNP範囲 を有するゲノムの全長 − Σ(除外されたLOH領域の長さ)
T5アッセイのためのSNP範囲を有するゲノムの全長は2.78E+09塩基対である。
Claims (11)
- a)
i.BRCA1及びBRCA2突然変異状態、及び
ii.ゲノムの各染色体に沿った複数の単一ヌクレオチドのホモ接合性またはヘテロ接合性
を含む癌患者の腫瘍に関するコンピュータシステムからのデータを受領すること;
b)前記データが:
iii.BRCA1もしくはBRCA2における1つ以上の有害な突然変異、または
iv.ゲノム全長によって除された各個々のLOH領域の長さの合計によって決定される約10%超のLOHを有するゲノムの割合(ここでLOH領域は、複数の近接単一ヌクレオチドにおけるホモ接合性の存在と定義されるが、染色体全体のLOHは除外する)を含む場合、PARP阻害剤に応答する可能性があるとしてコンピュータシステムによって前記癌患者を分類すること;及び
c)分類が工程b)の基準を満たす前記癌患者に対してPARP阻害剤の治療有効量を投与すること、
を含む、PARP阻害剤によって癌患者を治療する方法。 - 前記PARP阻害剤が、ルカパリブである請求項1に記載の方法。
- 前記癌が、乳癌、卵巣癌、または膵臓癌である請求項1に記載の方法。
- 前記癌が、乳癌である請求項3に記載の方法。
- 前記乳癌が、三重陰性乳癌である請求項4に記載の方法。
- 前記癌が、卵巣癌である請求項3に記載の方法。
- 前記卵巣癌が、高悪性度漿液性卵巣癌である請求項6に記載の方法。
- 前記癌が、膵臓癌である請求項3に記載の方法。
- ゲノム全長によって除された各個々のLOH領域の長さの合計によって決定されるLOHを有するゲノムの割合が、約11%超、約12%超、約13%超、約14%超、約15%超、約16%超、約17%超、約18%超、約19%超、または約20%超である請求項1に記載の方法。
- a)ゲノムの各染色体に沿った複数の単一ヌクレオチドのホモ接合性またはヘテロ接合性を含む癌患者の腫瘍に関するコンピュータシステムからのデータを受領すること;
b)前記データが、ゲノム全長によって除された各個々のLOH領域の長さの合計によって決定される約10%超のLOHを有するゲノムの割合(ここでLOH領域は複数の近接単一ヌクレオチドにおけるホモ接合性の存在と定義されるが、染色体全体のLOHは除外する)を含む場合、PARP阻害剤に応答する可能性があるとして前記コンピュータシステムによって前記癌患者を分類すること;及び
c)分類が工程b)の基準を満たす前記癌患者に対してPARP阻害剤の治療有効量を投与すること、
を含む、PARP阻害剤によって癌患者を治療する方法。 - ゲノム全長によって除された各個々のLOH領域の長さの合計によって決定されるLOHを有するゲノムの割合が、約11%超、約12%超、約13%超、約14%超、約15%超、約16%超、約17%超、約18%超、約19%超、または約20%超である請求項10に記載の方法。
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
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US201461928326P | 2014-01-16 | 2014-01-16 | |
US61/928,326 | 2014-01-16 | ||
US201462004424P | 2014-05-29 | 2014-05-29 | |
US62/004,424 | 2014-05-29 | ||
US201462039516P | 2014-08-20 | 2014-08-20 | |
US62/039,516 | 2014-08-20 | ||
US201462076165P | 2014-11-06 | 2014-11-06 | |
US62/076,165 | 2014-11-06 | ||
PCT/US2015/011413 WO2015108986A1 (en) | 2014-01-16 | 2015-01-14 | Use of parp inhibitors to treat breast or ovarian cancer patients showing a loss of heterozygosity |
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JP2017504623A5 JP2017504623A5 (ja) | 2018-02-22 |
JP6663350B2 JP6663350B2 (ja) | 2020-03-11 |
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US (1) | US20180163271A1 (ja) |
EP (1) | EP3094752A4 (ja) |
JP (1) | JP6663350B2 (ja) |
CN (1) | CN105917007A (ja) |
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JP2020519621A (ja) * | 2017-05-09 | 2020-07-02 | テサロ, インコーポレイテッド | 癌を治療するための併用療法 |
JP2020535814A (ja) * | 2017-09-28 | 2020-12-10 | インパクト−バイオ リミテッド | 阻害性キメラ抗原受容体(iCAR)を調製するための普遍的プラットフォーム |
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US11661453B2 (en) | 2017-09-30 | 2023-05-30 | Tesaro, Inc. | Combination therapies for treating cancer with niraparib and PD-1 inhibitors |
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CA3080441A1 (en) | 2012-02-23 | 2013-09-06 | The Children's Hospital Corporation | Methods for predicting anti-cancer response |
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JP6763114B2 (ja) * | 2016-06-02 | 2020-09-30 | 国立大学法人 琉球大学 | オオフトモモ抽出物を含むparp阻害剤 |
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MX2020007060A (es) | 2018-01-05 | 2020-11-11 | Cybrexa 1 Inc | Compuestos, composiciones y metodos para tratar enfermedades que involucren tejidos con enfermedades acidas o hipoxicas. |
WO2019195443A1 (en) * | 2018-04-04 | 2019-10-10 | The Wistar Institute Of Anatomy And Biology | Methods of treating cancers overexpressing carm1 with ezh2 inhibitors and a parp inhibitor |
US20220098196A1 (en) * | 2019-02-05 | 2022-03-31 | The Board Of Regents Of The University Of Texas System | Trapping-free parp inhibitors |
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KR20230002487A (ko) | 2020-04-28 | 2023-01-05 | 리젠 파마슈티컬스 아게 | 폴리(adp-리보스) 폴리머라제(parp) 억제제로서 유용한 신규 화합물 |
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WO2015108986A1 (en) | 2015-07-23 |
CN105917007A (zh) | 2016-08-31 |
EP3094752A1 (en) | 2016-11-23 |
US20180163271A1 (en) | 2018-06-14 |
EP3094752A4 (en) | 2017-08-16 |
JP6663350B2 (ja) | 2020-03-11 |
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