JPWO2020176620A5 - - Google Patents

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JPWO2020176620A5
JPWO2020176620A5 JP2021550012A JP2021550012A JPWO2020176620A5 JP WO2020176620 A5 JPWO2020176620 A5 JP WO2020176620A5 JP 2021550012 A JP2021550012 A JP 2021550012A JP 2021550012 A JP2021550012 A JP 2021550012A JP WO2020176620 A5 JPWO2020176620 A5 JP WO2020176620A5
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cancer
genes
therapy
hpv
algorithm
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ヒト対象における第1の癌状態および第2の癌状態を識別するための方法であって、前記第1の癌状態は、ヒトパピローマウイルス(HPV)発癌性ウイルスによる感染に関連する子宮頸癌、またはHPVによる感染に関連する頭頸部癌であり、前記第2の癌状態は、HPVを含まない状態に関連する子宮頸癌、またはHPVを含まない状態に関連する頭頸部癌であり、前記方法は、
(A)前記対象についてのデータセットを取得することであって、前記データセットは前記対象由来の複数の存在量値を含み、
前記複数の存在量値における各それぞれの存在量値は、前記対象由来の癌性組織における、複数の遺伝子における、対応する遺伝子の発現のレベルを定量化し、
前記複数の遺伝子は、表3に記載の遺伝子から選択される少なくとも10個の遺伝子を含む、取得することと、
(B)前記複数の遺伝子の前記存在量値に基づいて、少なくとも前記第1の癌状態および前記第2の癌状態を識別するように訓練された分類器に前記データセットを入力することと、を含む、方法。
1. A method for identifying a first cancer condition and a second cancer condition in a human subject, wherein the first cancer condition is cervical cancer associated with infection with the human papillomavirus (HPV) oncogenic virus; or head and neck cancer associated with infection by HPV, wherein said second cancer condition is cervical cancer associated with HPV-free conditions or head and neck cancer associated with HPV-free conditions , said method comprising: ,
(A) obtaining a dataset for the subject, the dataset comprising a plurality of abundance values from the subject;
each respective abundance value in the plurality of abundance values quantifies the level of expression of a corresponding gene in a plurality of genes in cancerous tissue from the subject;
obtaining, wherein the plurality of genes comprises at least 10 genes selected from the genes listed in Table 3;
(B) inputting the dataset into a classifier trained to distinguish at least the first cancer state and the second cancer state based on the abundance values of the plurality of genes; A method, including
前記複数の遺伝子が、表3に記載の遺伝子から選択される少なくとも20個の遺伝子を含む、請求項1に記載の方法。 2. The method of claim 1 , wherein said plurality of genes comprises at least 20 genes selected from the genes listed in Table 3. 前記複数の遺伝子が、少なくとも表3に記載の遺伝子の24個すべてを含む、請求項1に記載の方法。 2. The method of claim 1 , wherein said plurality of genes includes at least all 24 of the genes listed in Table 3. 前記複数の遺伝子が、300個以下の遺伝子を含む、請求項1~3のいずれか一項に記載の方法。4. The method of any one of claims 1-3, wherein the plurality of genes comprises 300 genes or less. 前記ヒト癌患者由来の前記癌性組織の試料のRNA配列決定によって前記複数の存在量値を決定することをさらに含む、請求項1~4のいずれか一項に記載の方法。 5. The method of any one of claims 1-4 , further comprising determining the plurality of abundance values by RNA sequencing of a sample of the cancerous tissue from the human cancer patient. 前記データセットが、前記対象由来の前記癌性組織の前記ゲノムにおける1つ以上の遺伝子座での1つ以上の対立遺伝子についての変異対立遺伝子カウントをさらに含む、請求項1~5のいずれか一項に記載の方法。 6. The data set of any one of claims 1-5 , wherein the dataset further comprises variant allele counts for one or more alleles at one or more loci in the genome of the cancerous tissue from the subject. The method described in section. 前記1つ以上の変異対立遺伝子が、TP53(ENSG00000141510)またはCDKN2A(ENSG00000147889)遺伝子における変異対立遺伝子から選択される、請求項6に記載の方法。 7. The method of claim 6 , wherein said one or more mutant alleles are selected from mutant alleles in the TP53 (ENSG00000141510) or CDKN2A (ENSG00000147889) genes. 前記分類器が、ロジスティック回帰アルゴリズム、ニューラルネットワークアルゴリズム、畳み込みニューラルネットワークアルゴリズム、サポートベクトルマシンアルゴリズム、ナイーブベイズアルゴリズム、最近傍アルゴリズム、ブーストツリーアルゴリズム、ランダムフォレストアルゴリズム、決定木アルゴリズム、またはクラスタリングアルゴリズムである、請求項1~7のいずれか一項に記載の方法。 wherein said classifier is a logistic regression algorithm, a neural network algorithm, a convolutional neural network algorithm, a support vector machine algorithm, a Naive Bayes algorithm, a nearest neighbor algorithm, a boosted tree algorithm, a random forest algorithm, a decision tree algorithm, or a clustering algorithm; Item 8. The method according to any one of Items 1 to 7 . 前記分類器の結果が、前記ヒト癌患者がHPV発癌性ウイルスに感染していることを示す場合、HPV感染に関連する子宮頸癌または頭頸部癌の治療のために調整された第1の療法を割り当てること、およびA first therapy tailored for the treatment of cervical cancer or head and neck cancer associated with HPV infection if the results of the classifier indicate that the human cancer patient is infected with the HPV oncogenic virus. and
前記分類器の結果が、前記ヒト癌患者がHPV発癌性ウイルスに感染していないことを示す場合、HPV感染に関連しない子宮頸癌または頭頸部癌の治療のために調整された第2の療法を割り当てること、A second therapy tailored for the treatment of cervical or head and neck cancer not associated with HPV infection if the results of the classifier indicate that the human cancer patient is free of HPV oncogenic virus. to assign
によって、子宮頸癌または頭頸部癌のための療法を割り当てることをさらに含む、請求項1~8のいずれか一項に記載の方法。The method of any one of claims 1-8, further comprising allocating therapy for cervical cancer or head and neck cancer by.
HPV感染に関連する子宮頸癌の治療のために調整された前記第1の療法が、治療用ワクチンまたは養子細胞治療である、請求項9に記載の方法。 10. The method of claim 9 , wherein said first therapy tailored for the treatment of cervical cancer associated with HPV infection is therapeutic vaccine or adoptive cell therapy . HPV感染に関連しない子宮頸癌の治療のために調整された前記第2の療法が、化学療法である、請求項9または10に記載の方法。 11. The method of claim 9 or 10 , wherein said second therapy adjusted for treatment of cervical cancer not associated with HPV infection is chemotherapy. HPV感染に関連する頭頸部癌の治療のために調整された前記第1の療法が、治療用ワクチン、免疫チェックポイント阻害剤、またはPI3K阻害剤である、請求項9に記載の方法。 10. The method of claim 9 , wherein said first therapy adjusted for the treatment of head and neck cancer associated with HPV infection is a therapeutic vaccine , immune checkpoint inhibitor, or PI3K inhibitor . HPV感染に関連しない頭頸部癌の治療のために調整された前記第2の療法が、化学療法である、請求項9または12に記載の方法。 13. The method of claim 9 or 12 , wherein said second therapy adjusted for treatment of head and neck cancer not associated with HPV infection is chemotherapy. 前記化学療法が、シスプラチンの投与を含む、請求項11または13に記載の方法。 14. The method of claim 11 or 13 , wherein said chemotherapy comprises administration of cisplatin. 子宮頸癌の治療のために調整された前記第2の療法が、5-フルオロウラシル、パクリタキセル、およびベバシズマブからなる群から選択される第2の治療薬の共投与をさらに含む、請求項14に記載の方法。 15. The claim 14 , wherein said second therapy adjusted for treatment of cervical cancer further comprises co-administration of a second therapeutic agent selected from the group consisting of 5-fluorouracil, paclitaxel, and bevacizumab. the method of. 頭頸部癌の治療のために調整された前記第2の療法が、同時放射線療法または術後化学放射線療法をさらに含む、請求項14に記載の方法。 15. The method of claim 14 , wherein said second therapy adjusted for treatment of head and neck cancer further comprises concurrent radiotherapy or postoperative chemoradiation therapy.
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