JP2015505830A - タキサン療法を用いて乳癌を処置する方法 - Google Patents
タキサン療法を用いて乳癌を処置する方法 Download PDFInfo
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Abstract
Description
この出願は、2011年11月30日に出願されたU.S.S.N.61/565,133、及び2012年4月18日に出願されたU.S.S.N.61/635,048の優先権及び利益を主張する。これらの出願のそれぞれの内容の全体を参照により本明細書中に援用する。
本開示は、概して、癌生物学の分野に関し、詳細には、特定の癌細胞表現型の検出及び同定、ならびに適切な療法との相関の分野に関する。
本開示は、タキサン又はタキサン誘導体を含む乳癌処置が、乳癌に罹患している患者に投与するのに最適であるか否かを決定する方法を提供する。乳癌患者が、タキサン又はタキサン誘導体を含む処置を受けるべきであるか否かの決定は、固有遺伝子発現セットを用いた乳癌の増殖シグネチャーの決定を含む。本開示はまた、乳癌患者が、タキサン又はタキサン誘導体を含む処置を受けるべきであるか否かを決定し、そしてこの決定に基づいて患者に最適な乳癌処置を施すことによって乳癌を治療する方法を提供する。
本発明の方法は、ANLN、CCNB1、CCNE1、CDC20、CDC6、CDCA1、CENPF、CEP55、EXO1、KIF2C、KNTC2、MELK、MKI67、ORC6L、PTTG1、RRM2、TYMS、UBE2C及び/又はUBE2Tから選択されるPAM50固有遺伝子から成る19種類の遺伝子サブセットのうちの少なくとも1種類、それらの組み合わせ、又はそのそれぞれの発現を測定することを含み得る。
本発明の方法は、ANLN、CCNE1、CDC20、CDC6、CDCA1、CENPF、CEP55、EXO1、KIF2C、KNTC2、MELK、MKI67、ORC6L、PTTG1、RRM2、TYMS、UBE2C及び/又はUBE2Tから選択されるPAM50固有遺伝子から成る19種類の遺伝子サブセットのうちの少なくとも1種類、それらの組み合わせ、又はそのそれぞれの発現を測定することを含み得る。
本発明の方法は、から選択されるPAM50固有遺伝子から成る18種類の遺伝子サブセットのうちの少なくとも1種類、それらの組み合わせ、又はそのそれぞれの発現を測定することを含み得る。
本発明の方法は、BIRC5、CCNB1、CDC20、CDCA1/NUF2、CEP55、KNTC2/NDC80、MKI67、PTTG1、RRM2、TYMS及び/又はUBE2Cから選択されるPAM50固有遺伝子から成る11種類の遺伝子サブセットのうちの少なくとも1種類、それらの組み合わせ、又はそのそれぞれの発現を測定することを含み得る。
本発明の方法は、ANLN、CCNB1、CDC20、CENPF、CEP55、KIF2C、MKI67、MYBL2、RRM2及び/又はUBE2Cから選択されるPAM50固有遺伝子から成る10種類の遺伝子サブセットのうちの少なくとも1種類、それらの組み合わせ、又はそのそれぞれの発現を測定することを含み得る。
式中、変数「基底」、「Her2」、「LumA」、「LumB」、及び「正常」は、試験サンプルからの発現プロフィールが、Gene Expression Omnibus(GEO)に預けられた遺伝子発現データを用いて作成されたセントロイドに対して比較されたときのそれぞれのクラシファイアのセントロイドに対する距離である。
ROR(完全)=0.05*基底+0.1*Her2+−0.19*LumA+0.05*LumB+−0.09*正常+0.16*T+0.08*N
同様に、試験発現プロフィールが、アクセッション番号GSE2845としてGEOに預けられた遺伝子発現データを用いて作成されたセントロイドに対して比較されたときのものである。
式中、変数「基底」、「Her2」、「LumA」、及び「LumB」は、上記説明の通りであり、試験発現プロフィールが、アクセッション番号GSE2845としてGEOに預けられた遺伝子発現データを用いて作成されたセントロイドに対して比較される。なお別の実施形態では、リスクスコアは、以下の式(変数は上記説明のとおりである)を用いて、乳癌サブタイプと臨床的変数である腫瘍サイズ(T)との組み合わせを用いて計算することもできる:
ROR−C=0.05*基底+0.11*Her2+−0.23*LumA+0.09*LumB+0.17*T。
式中、変数「基底」、「Her2」、「LumA」、「LumB」、及び「Prolif」は、上記説明の通りであり、試験発現プロフィールが、アクセッション番号GSE2845としてGEOに預けられた遺伝子発現データを用いて作成されたセントロイドに対して比較される。なお別の実施形態では、リスクスコアは、以下の式(変数は上記説明のとおりである)を用いて、乳癌サブタイプ、増殖シグネチャー及び臨床的変数である腫瘍サイズ(T)との組み合わせを用いて計算することもできる:
ROR−PT=−0.001*基底+0.73*Her2+−0.9*LumA+0.05*LumB+0.13*T+0.33*Prolif。
患者、サンプル及び臨床データ
Ki67スコアは核染色で総数の腫瘍細胞のパーセンテージに規定された。
Claims (24)
- 乳癌の処置を必要とする対象の乳癌を処置する方法であって、以下のステップ:
(a)前記対象からのサンプルを準備し;
(b)前記サンプルにおける、表1のうちの少なくとも1種類の遺伝子の発現を測定し;
(c)前記サンプルにおける前記少なくとも1種類の遺伝子の発現に基づく増殖シグネチャーを決定し;そして
(d)乳癌処置を対象に投与すること、を含み、
前記サンプルが、低い増殖シグネチャーを有していると分類される場合は、毎週投与する、タキサン又はタキサン誘導体を含んで成る乳癌処置を前記対象に与え、前記サンプルが低い増殖シグネチャーを有していないと分類される場合は、毎週投与する、タキサン又はタキサン誘導体を含まない乳癌処置を前記対象に与え、これにより、前記対象の乳癌を処置する、方法。 - 乳癌の処置を必要とする対象における、毎週投与される、タキサン又はタキサン誘導体を含んで成る乳癌処置の有効性の見込みをスクリーニングする方法であって、以下のステップ:
(a)前記対象からのサンプルを準備し;
(b)前記サンプルにおける、表1のうちの少なくとも1種類の遺伝子の発現を測定し;そして
(c)前記サンプルにおける前記少なくとも1種類の遺伝子の発現に基づく増殖シグネチャーを決定する、を含み、
前記サンプルが、低い増殖シグネチャーを有していると分類される場合は、毎週投与される、タキサン又はタキサン誘導体を含んで成る乳癌処置が、対象で有効である傾向がより強い、方法。 - ANLN、BIRC5、CCNB1、CCNE1、CDC20、CDC6、CDCA1、CENPF、CEP55、EXO1、KIF2C、KNTC2、MELK、MKI67、MYBL2、ORC6L、PTTG1、RRM2、TYMS、UBE2C、及びUBE2Tから選択される少なくとも1種類の遺伝子の発現を測定することを含む、請求項1又は2に記載の方法。
- ANLN、BIRC5、CCNB1、CCNE1、CDC20、CDC6、CDCA1、CENPF、CEP55、EXO1、KIF2C、KNTC2、MELK、MKI67、MYBL2、ORC6L、PTTG1、RRM2、TYMS、UBE2C、及びUBE2Tから選択される遺伝子のそれぞれの発現を測定することを含む、請求項1又は2に記載の方法。
- ANLN、CCNE1、CDC20、CDC6、CDCA1、CENPF、CEP55、EXO1、KIF2C、KNTC2、MELK、MKI67、ORC6L、PTTG1、RRM2、TYMS、UBE2C、及びUBE2Tから選択される少なくとも1種類の遺伝子の発現を測定することを含む、請求項1又は2に記載の方法。
- ANLN、CCNE1、CDC20、CDC6、CDCA1、CENPF、CEP55、EXO1、KIF2C、KNTC2、MELK、MKI67、ORC6L、PTTG1、RRM2、TYMS、UBE2C、及びUBE2Tから選択される遺伝子のそれぞれの発現を測定することを含む、請求項1又は2に記載の方法。
- BIRC5、CCNB1、CDC20、CDCA1/NUF2、CEP55、KNTC2/NDC80、MKI67、PTTG1、RRM2、TYMS、及びUBE2Cから選択される少なくとも1種類の遺伝子の発現を測定することを含む、請求項1又は2に記載の方法。
- BIRC5、CCNB1、CDC20、CDCA1/NUF2、CEP55、KNTC2/NDC80、MKI67、PTTG1、RRM2、TYMS、及びUBE2Cから選択される遺伝子のそれぞれの発現を測定することを含む、請求項1又は2に記載の方法。
- ANLN、CCNB1、CDC20、CENPF、CEP55、KIF2C、MKI67、MYBL2、RRM2、及びUBE2Cから選択される少なくとも1種類の遺伝子の発現を測定することを含む、請求項1又は2に記載の方法。
- ANLN、CCNB1、CDC20、CENPF、CEP55、KIF2C、MKI67、MYBL2、RRM2、及びUBE2Cから選択される遺伝子のそれぞれの発現を測定することを含む、請求項1又は2に記載の方法。
- 前記タキサン又はタキサン誘導体が、パクリタキセルである、請求項1又は2に記載の方法。
- 前記タキサン又はタキサン誘導体を含んで成る乳癌処置が、アントラサイクリン、シクロホスファミド、及び5−フルオロウラシルから成る群のうちの1若しくは複数のメンバーをさらに含んで成る、請求項1又は2に記載の方法。
- 前記アントラサイクリンが、ドキソルビシン及びエピルビシンから成る群から選択される、請求項12に記載の方法。
- タキサン又はタキサン誘導体を、アントラサイクリン、シクロホスファミド又は5−フルオロウラシルの投与前又は投与後に投与する、請求項12に記載の方法。
- 前記タキサン又はタキサン誘導体を含んで成る乳癌処置が、アントラサイクリン、シクロホスファミド、及び5−フルオロウラシルから成る群のメンバーのそれぞれをさらに含んで成る、請求項1又は2に記載の方法。
- 前記アントラサイクリンが、ドキソルビシン及びエピルビシンから成る群から選択される、請求項15に記載の方法。
- タキサン又はタキサン誘導体を、アントラサイクリン、シクロホスファミド、及び5−フルオロウラシルの投与前、投与後又はそれらの投与と同時に投与する、請求項15に記載の方法。
- 次の:腫瘍の大きさ、腫瘍のグレード、結節状態、固有サブタイプ、エストロゲン受容体発現、プロゲステロン受容体発現、及びHER2/ERBB2発現、のうちの少なくとも1種類を測定することをさらに含む、請求項1又は2に記載の方法。
- 次の:腫瘍の大きさ、腫瘍のグレード、結節状態、固有サブタイプ、エストロゲン受容体発現、プロゲステロン受容体発現、及びHER2/ERBB2発現、のそれぞれを測定することをさらに含む、請求項1又は2に記載の方法。
- 前記サンプルが、細胞又は組織の抽出サンプルである、請求項1又は2に記載の方法。
- 前記組織を生検から得る、請求項1又は2に記載の方法。
- 前記サンプルが、体液の抽出サンプルである、請求項1又は2に記載の方法。
- 前記体液が、血液、リンパ液、尿、唾液、及びニップル吸引液から成る群から選択される、請求項22に記載の方法。
- 前記少なくとも1種類の遺伝子の発現を、ナノレポーターコードシステムを使用して測定する、請求項1又は2に記載の方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017538115A (ja) * | 2014-11-24 | 2017-12-21 | ナノストリング テクノロジーズ,インコーポレイティド | 遺伝子精製および画像化のための方法および装置 |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2009262894B2 (en) | 2008-05-30 | 2014-01-30 | British Columbia Cancer Agency Branch | Gene expression profiles to predict breast cancer outcomes |
JP5971769B2 (ja) | 2011-03-15 | 2016-08-17 | ザ ユニバーシティー オブ ノースカロライナ アット チャペル ヒル | アントラサイクリン療法を用いて乳癌を処置する方法 |
EA028452B1 (ru) | 2011-07-29 | 2017-11-30 | Медивейшн Простейт Терапьютикс, Инк. | Лечение рака молочной железы |
JP2016519935A (ja) * | 2013-05-13 | 2016-07-11 | ナノストリング テクノロジーズ,インコーポレイティド | 結節陽性の初期乳癌における再発リスクを予測する方法 |
SG11201601060RA (en) * | 2013-08-19 | 2016-03-30 | Biontech Diagnostics Gmbh | Methods and kits for the molecular subtyping of tumors |
US20150072021A1 (en) * | 2013-09-09 | 2015-03-12 | British Columbia Cancer Agency Branch | Methods and Kits for Predicting Outcome and Methods and Kits for Treating Breast Cancer with Radiation Therapy |
US20170298443A1 (en) * | 2014-09-25 | 2017-10-19 | Moffitt Genetics Corporation | Prognostic tumor biomarkers |
EP3221469B1 (en) | 2014-11-21 | 2020-01-15 | Nanostring Technologies, Inc | Enzyme- and amplification-free sequencing |
CA2969163A1 (en) * | 2014-12-09 | 2016-06-16 | King's College London | Breast cancer treatment with taxane therapy |
EP3230471B1 (en) | 2014-12-12 | 2019-08-28 | Medivation Prostate Therapeutics LLC | Method for predicting response to breast cancer therapeutic agents and method of treatment of breast cancer |
EP4324929A1 (en) | 2016-05-16 | 2024-02-21 | Nanostring Technologies, Inc. | Methods for detecting target nucleic acids in a sample |
US10934590B2 (en) | 2016-05-24 | 2021-03-02 | Wisconsin Alumni Research Foundation | Biomarkers for breast cancer and methods of use thereof |
CN110225980B (zh) | 2016-11-21 | 2023-01-06 | 纳米线科技公司 | 化学组合物及其使用方法 |
WO2019023551A1 (en) * | 2017-07-28 | 2019-01-31 | Nanostring Technologies, Inc. | IMMUNO-ONCOLOGY BIOMARKERS AND METHODS OF USE |
CA3099909A1 (en) | 2018-05-14 | 2019-11-21 | Nanostring Technologies, Inc. | Chemical compositions and methods of using same |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011524162A (ja) * | 2008-05-30 | 2011-09-01 | ザ ユニバーシティー オブ ノースカロライナ アット チャペル ヒル | 乳癌の予後を予測するための遺伝子発現プロフィール |
US20110286960A1 (en) * | 2008-11-02 | 2011-11-24 | Optimata Ltd. | Cancer therapy by docetaxel and granulocyte colony-stimulating factor (g-csf) |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1631689A2 (en) * | 2003-05-28 | 2006-03-08 | Genomic Health, Inc. | Gene expression markers for predicting response to chemotherapy |
ES2550614T3 (es) * | 2004-04-09 | 2015-11-11 | Genomic Health, Inc. | Marcadores de expresión génica para predecir la respuesta a la quimioterapia |
US20090299640A1 (en) | 2005-11-23 | 2009-12-03 | University Of Utah Research Foundation | Methods and Compositions Involving Intrinsic Genes |
ATE525482T1 (de) * | 2005-12-23 | 2011-10-15 | Nanostring Technologies Inc | Nanoreporter und verfahren zu deren herstellung und verwendung |
WO2008006517A2 (en) | 2006-07-13 | 2008-01-17 | Siemens Healthcare Diagnostics Gmbh | Prediction of breast cancer response to taxane-based chemotherapy |
US20090105167A1 (en) | 2007-10-19 | 2009-04-23 | Duke University | Predicting responsiveness to cancer therapeutics |
EP3216874A1 (en) | 2008-09-05 | 2017-09-13 | TOMA Biosciences, Inc. | Methods for stratifying and annotating cancer drug treatment options |
CA2807557C (en) * | 2009-08-06 | 2019-09-17 | Partha S. Ray | Diagnosis of primary and metastatic basal-like breast cancer and other cancer types |
EP2507396A4 (en) | 2009-12-01 | 2013-06-19 | Precision Therapeutics Inc | MULTI-MEDICATION RESPONSE MARKERS FOR BREAST CANCER CELLS |
WO2011130495A1 (en) * | 2010-04-14 | 2011-10-20 | Nuvera Biosciences, Inc. | Methods of evaluating response to cancer therapy |
JP5971769B2 (ja) | 2011-03-15 | 2016-08-17 | ザ ユニバーシティー オブ ノースカロライナ アット チャペル ヒル | アントラサイクリン療法を用いて乳癌を処置する方法 |
EP2723897A4 (en) * | 2011-06-24 | 2015-03-18 | Nanostring Technologies Inc | MULTIVARIATED DIAGNOSTIC ASSAYS AND METHODS OF USE THEREOF |
CN104704128A (zh) | 2012-05-22 | 2015-06-10 | 纳米线科技公司 | 预测乳腺癌结果的nano46基因和方法 |
CA2877378A1 (en) | 2012-06-29 | 2014-01-03 | Nanostring Technologies, Inc. | Methods of treating breast cancer with gemcitabine therapy |
-
2012
- 2012-11-30 WO PCT/US2012/067317 patent/WO2013082440A2/en active Application Filing
- 2012-11-30 AU AU2012345789A patent/AU2012345789B2/en not_active Expired - Fee Related
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-
2014
- 2014-05-29 IL IL232885A patent/IL232885A0/en unknown
-
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-
2017
- 2017-05-10 JP JP2017093705A patent/JP2017214360A/ja active Pending
- 2017-08-10 IL IL253947A patent/IL253947A0/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011524162A (ja) * | 2008-05-30 | 2011-09-01 | ザ ユニバーシティー オブ ノースカロライナ アット チャペル ヒル | 乳癌の予後を予測するための遺伝子発現プロフィール |
US20110286960A1 (en) * | 2008-11-02 | 2011-11-24 | Optimata Ltd. | Cancer therapy by docetaxel and granulocyte colony-stimulating factor (g-csf) |
Non-Patent Citations (2)
Title |
---|
CLIN. CANCER RES., vol. 16, no. 21, JPN7016001609, 2010, pages 5222 - 5232, ISSN: 0003340111 * |
JOURNAL OF CLINICAL ONCOLOGY, vol. 27, no. 8, JPN7016001608, 2009, pages 1160 - 1167, ISSN: 0003340110 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2017538115A (ja) * | 2014-11-24 | 2017-12-21 | ナノストリング テクノロジーズ,インコーポレイティド | 遺伝子精製および画像化のための方法および装置 |
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