JPWO2020014581A5 - - Google Patents
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- JPWO2020014581A5 JPWO2020014581A5 JP2021500545A JP2021500545A JPWO2020014581A5 JP WO2020014581 A5 JPWO2020014581 A5 JP WO2020014581A5 JP 2021500545 A JP2021500545 A JP 2021500545A JP 2021500545 A JP2021500545 A JP 2021500545A JP WO2020014581 A5 JPWO2020014581 A5 JP WO2020014581A5
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- cancer
- pharmaceutical composition
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- gsk3α
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- 201000011510 cancer Diseases 0.000 claims description 70
- 101700074239 GSK3A Proteins 0.000 claims description 32
- 102100004323 ASPG Human genes 0.000 claims description 20
- 230000035772 mutation Effects 0.000 claims description 20
- 229960003272 ASPARAGINASE Drugs 0.000 claims description 18
- 108010024976 Asparaginase Proteins 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 12
- 239000000523 sample Substances 0.000 claims description 10
- 102100002069 GSK3A Human genes 0.000 claims description 8
- 102100016246 RNF43 Human genes 0.000 claims description 8
- 101700048059 RNF43 Proteins 0.000 claims description 8
- 102100003835 RSPO1 Human genes 0.000 claims description 8
- 101700039152 RSPO1 Proteins 0.000 claims description 8
- 102100003836 RSPO2 Human genes 0.000 claims description 8
- 101700028308 RSPO2 Proteins 0.000 claims description 8
- 102100003837 RSPO3 Human genes 0.000 claims description 8
- 101700028929 RSPO3 Proteins 0.000 claims description 8
- 102100003838 RSPO4 Human genes 0.000 claims description 8
- 101700030228 RSPO4 Proteins 0.000 claims description 8
- 239000012472 biological sample Substances 0.000 claims description 8
- 206010024324 Leukaemias Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 150000003384 small molecules Chemical class 0.000 claims description 6
- 206010000880 Acute myeloid leukaemia Diseases 0.000 claims description 4
- 210000004369 Blood Anatomy 0.000 claims description 4
- AQGNHMOJWBZFQQ-UHFFFAOYSA-N CT 99021 Chemical compound CC1=CNC(C=2C(=NC(NCCNC=3N=CC(=CC=3)C#N)=NC=2)C=2C(=CC(Cl)=CC=2)Cl)=N1 AQGNHMOJWBZFQQ-UHFFFAOYSA-N 0.000 claims description 4
- 206010008958 Chronic lymphocytic leukaemia Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000000429 Leukemia, Lymphocytic, Chronic, B-Cell Diseases 0.000 claims description 4
- 208000008456 Leukemia, Myelogenous, Chronic, BCR-ABL Positive Diseases 0.000 claims description 4
- 208000007046 Leukemia, Myeloid, Acute Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010025650 Malignant melanoma Diseases 0.000 claims description 4
- 206010061289 Metastatic neoplasm Diseases 0.000 claims description 4
- 206010025310 Other lymphomas Diseases 0.000 claims description 4
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 230000025458 RNA interference Effects 0.000 claims description 4
- 206010039491 Sarcoma Diseases 0.000 claims description 4
- PMJIHLSCWIDGMD-UHFFFAOYSA-N Tideglusib Chemical compound O=C1SN(C=2C3=CC=CC=C3C=CC=2)C(=O)N1CC1=CC=CC=C1 PMJIHLSCWIDGMD-UHFFFAOYSA-N 0.000 claims description 4
- 201000005510 acute lymphocytic leukemia Diseases 0.000 claims description 4
- 230000001093 anti-cancer Effects 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 201000006934 chronic myeloid leukemia Diseases 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 108010049611 glycogen synthase kinase 3 alpha Proteins 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 230000001394 metastastic Effects 0.000 claims description 4
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 229960001744 pegaspargase Drugs 0.000 claims description 4
- 108010001564 pegaspargase Proteins 0.000 claims description 4
- 210000001519 tissues Anatomy 0.000 claims description 4
- 238000004166 bioassay Methods 0.000 claims description 3
- JULOXTBHCHEFBE-ISLYRVAYSA-N (3E)-3-[5-(morpholin-4-ylmethyl)-1H-pyridin-2-ylidene]-2-oxo-1H-indole-5-carbonitrile Chemical compound O=C1NC2=CC=C(C#N)C=C2\C1=C(C=C1)/NC=C1CN1CCOCC1 JULOXTBHCHEFBE-ISLYRVAYSA-N 0.000 claims description 2
- XLSYZSRXVVCHLS-UHFFFAOYSA-N 1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[1,2-c]pyrazol-5-yl]-3-morpholin-4-ylurea Chemical compound C1CN(CCOC)CCN1CC1=CC=C(C=2C=3C(=O)C4=C(NC(=O)NN5CCOCC5)C=CC=C4C=3NN=2)C=C1 XLSYZSRXVVCHLS-UHFFFAOYSA-N 0.000 claims description 2
- JCSGFHVFHSKIJH-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-4-(1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1C(C(NC1=O)=O)=C1C1=CC=C(Cl)C=C1Cl JCSGFHVFHSKIJH-UHFFFAOYSA-N 0.000 claims description 2
- PQCXVIPXISBFPN-UHFFFAOYSA-N 3-(3-chloro-4-hydroxyanilino)-4-(2-nitrophenyl)pyrrole-2,5-dione Chemical compound C1=C(Cl)C(O)=CC=C1NC1=C(C=2C(=CC=CC=2)[N+]([O-])=O)C(=O)NC1=O PQCXVIPXISBFPN-UHFFFAOYSA-N 0.000 claims description 2
- FARXPFGGGGLENU-UHFFFAOYSA-N 3-(5-fluoro-1-benzofuran-3-yl)-4-(5-methyl-[1,3]dioxolo[4,5-f]indol-7-yl)pyrrole-2,5-dione Chemical compound C12=CC=3OCOC=3C=C2N(C)C=C1C1=C(C=2C3=CC(F)=CC=C3OC=2)C(=O)NC1=O FARXPFGGGGLENU-UHFFFAOYSA-N 0.000 claims description 2
- WJRRGYBTGDJBFX-UHFFFAOYSA-N 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine Chemical compound CC(C)N1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(C)(=O)=O)=N1 WJRRGYBTGDJBFX-UHFFFAOYSA-N 0.000 claims description 2
- PAOFPNGYBWGKCO-UHFFFAOYSA-N 4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide;hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1C(=O)NC1=CNN=C1C(=O)NC1CCNCC1 PAOFPNGYBWGKCO-UHFFFAOYSA-N 0.000 claims description 2
- MDZCSIDIPDZWKL-UHFFFAOYSA-N 6-N-[2-[[4-(2,4-dichlorophenyl)-5-imidazol-1-ylpyrimidin-2-yl]amino]ethyl]-3-nitropyridine-2,6-diamine Chemical compound C1=C([N+]([O-])=O)C(N)=NC(NCCNC=2N=C(C(=CN=2)N2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1 MDZCSIDIPDZWKL-UHFFFAOYSA-N 0.000 claims description 2
- 108060005293 AGA Proteins 0.000 claims description 2
- 229950001573 Abemaciclib Drugs 0.000 claims description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 2
- 229940073038 Elspar Drugs 0.000 claims description 2
- 229940049769 Erwinia asparaginase Drugs 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- HRJWTAWVFDCTGO-UHFFFAOYSA-N LY2090314 Chemical compound C1CN(C=23)C=C(C=4C(NC(=O)C=4C=4N5C=CC=CC5=NC=4)=O)C3=CC(F)=CC=2CN1C(=O)N1CCCCC1 HRJWTAWVFDCTGO-UHFFFAOYSA-N 0.000 claims description 2
- UZWDCWONPYILKI-UHFFFAOYSA-N N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine Chemical compound C1CN(CC)CCN1CC(C=N1)=CC=C1NC1=NC=C(F)C(C=2C=C3N(C(C)C)C(C)=NC3=C(F)C=2)=N1 UZWDCWONPYILKI-UHFFFAOYSA-N 0.000 claims description 2
- HUXYBQXJVXOMKX-UHFFFAOYSA-N N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-c]pyrazol-3-yl]-3-methylbutanamide Chemical compound CC(C)CC(=O)NC1=NNC(C2(C)C)=C1CN2C(=O)C1CCN(C)CC1 HUXYBQXJVXOMKX-UHFFFAOYSA-N 0.000 claims description 2
- -1 OTS-167 Chemical compound 0.000 claims description 2
- 229920000272 Oligonucleotide Polymers 0.000 claims description 2
- 229940099216 Oncaspar Drugs 0.000 claims description 2
- 108020004459 Small Interfering RNA Proteins 0.000 claims description 2
- 229920001891 Small hairpin RNA Polymers 0.000 claims description 2
- 229950005284 Tideglusib Drugs 0.000 claims description 2
- 230000004156 Wnt signaling pathway Effects 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- 102000004965 antibodies Human genes 0.000 claims description 2
- 108090001123 antibodies Proteins 0.000 claims description 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 2
- 108010033937 calaspargase pegol Proteins 0.000 claims description 2
- 210000004027 cells Anatomy 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 238000001415 gene therapy Methods 0.000 claims description 2
- 238000010362 genome editing Methods 0.000 claims description 2
- 238000001794 hormone therapy Methods 0.000 claims description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 2
- 238000009169 immunotherapy Methods 0.000 claims description 2
- 229920001239 microRNA Polymers 0.000 claims description 2
- 239000002679 microRNA Substances 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 239000002924 silencing RNA Substances 0.000 claims description 2
- 239000004055 small Interfering RNA Substances 0.000 claims description 2
- 238000009168 stem cell therapy Methods 0.000 claims description 2
- 238000009580 stem-cell therapy Methods 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 238000002626 targeted therapy Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 38
- 239000000203 mixture Substances 0.000 claims 3
- 239000000463 material Substances 0.000 description 2
Description
単数形の「1つの(a)」、「1つの(an)」および「その(the)」は、文脈によって明らかに別のことが示される場合を除き、複数形の言及物を含む。同様に、「または」という語は、文脈によって明らかに別のことが示される場合を除き、「および」を含むものと意図される。本明細書において記載されるものと同様または同等な方法および材料を、本開示の実践または試験において用いることができるが、適切な方法および材料を以下に記載する。「例えば(e.g.)」という略号は、ラテン語のexempli gratiaに由来し、非限定的な例を示すために本明細書において用いられる。したがって「例えば(e.g.)」という略号は「例えば(for example)」という用語と同義である。
[本発明1001]
がんを有する対象にアスパラギナーゼとGSK3αを阻害する作用物質とを投与する段階を含む、がんを処置するための方法。
[本発明1002]
前記がんが、がん腫、黒色腫、肉腫、骨髄腫、白血病、およびリンパ腫からなるリストから選択される、本発明1001の方法。
[本発明1003]
前記がんが固形腫瘍である、本発明1001の方法。
[本発明1004]
前記白血病が、急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)、急性リンパ性白血病(ALL)、および慢性リンパ性白血病(CLL)である、本発明1002の方法。
[本発明1005]
前記がんがアスパラギナーゼに耐性である、本発明1001の方法。
[本発明1006]
前記がんがアスパラギナーゼに耐性ではない、本発明1001の方法。
[本発明1007]
前記アスパラギナーゼが、L-アスパラギナーゼ(Elspar)、ペグアスパルガーゼ(PEG-アスパラギナーゼ; Oncaspar)、SC-PEGアスパラギナーゼ(カラスパルガーゼペゴル)、およびエルウィニア（Erwinia）アスパラギナーゼ(エルウィナーゼ)からなる群より選択される、本発明1001の方法。
[本発明1008]
GSK3αを阻害する前記作用物質が、小分子、抗体、ペプチド、ゲノム編集システム、アンチセンスオリゴヌクレオチド、およびRNAiからなる群より選択される、本発明1001の方法。
[本発明1009]
前記小分子が、BRD0705、BRD4963、BRD1652、BRD3731、CHIR-98014、LY2090314、AZD1080、CHIR-99021 (CT99021) HCl、CHIR-99021 (CT99021)、BIO-アセトキシム、SB216763、SB415286、アベマシクリブ(LY2835210)、AT-9283、RGB-286638、PHA-793887、AT-7519、AZD-5438、OTS-167、9-ING-41、チデグルシブ(NP031112)、およびAR-A014418からなる群より選択される、本発明1008の方法。
[本発明1010]
前記小分子がBRD0705である、本発明1008の方法。
[本発明1011]
前記RNAiがマイクロRNA、siRNA、またはshRNAである、本発明1008の方法。
[本発明1012]
GSK3αを阻害することが、GSK3αの発現レベルおよび/または活性を阻害することである、本発明1001の方法。
[本発明1013]
GSK3αの前記発現レベルおよび/または活性が、適切な対照と比較して少なくとも50%、少なくとも60%、少なくとも70%、少なくとも80%、少なくとも90%、またはそれ以上阻害される、本発明1012の方法。
[本発明1014]
前記対象に抗がん療法が以前に実施されている、本発明1001の方法。
[本発明1015]
前記対象に抗がん療法が以前に実施されていない、本発明1001の方法。
[本発明1016]
投与する段階の前に、がんを有すると対象を診断する段階をさらに含む、本発明1001～1015のいずれかの方法。
[本発明1017]
投与する段階の前に、がんを有すると対象を診断するアッセイ法から結果を受け取る段階をさらに含む、本発明1001～1015のいずれかの方法。
[本発明1018]
GSK3αの阻害をもたらす変異を含むがんを有する対象に、アスパラギナーゼを投与する段階を含む、がんを処置するための方法。
[本発明1019]
前記変異が、がん細胞においてWNTシグナル伝達経路の活性化をもたらす、本発明1018の方法。
[本発明1020]
前記変異が、R-スポンジン1 (RSPO1)、R-スポンジン2 (RSPO2)、R-スポンジン3 (RSPO3)、R-スポンジン4 (RSPO4)、リングフィンガータンパク質43 (RNF43)、およびグリコーゲンシンターゼキナーゼ3α(GSK3A、より一般的にはGSK3αと呼ばれる)からなる群より選択される遺伝子中に存在する、本発明1018の方法。
[本発明1021]
前記変異が、R-スポンジン1 (RSPO1)、R-スポンジン2 (RSPO2)、R-スポンジン3 (RSPO3)、R-スポンジン4 (RSPO4)、リングフィンガータンパク質43 (RNF43)、およびグリコーゲンシンターゼキナーゼ3α(GSK3A、より一般的にはGSK3αと呼ばれる)からなる群より選択される遺伝子の発現を変化させる、本発明1018の方法。
[本発明1022]
前記がんが、がん腫、黒色腫、肉腫、骨髄腫、白血病、またはリンパ腫からなるリストから選択される、本発明1018の方法。
[本発明1023]
前記がんが固形腫瘍である、本発明1018の方法。
[本発明1024]
前記がんが結腸がんまたは膵臓がんである、本発明1018の方法。
[本発明1025]
前記がんが転移性である、本発明1018の方法。
[本発明1026]
投与の前に、前記対象が、GSK3αの阻害をもたらす変異を含むがんを有するとして同定される、本発明1018の方法。
[本発明1027]
前記変異が、前記対象から得られた生体サンプルにおいて同定される、本発明1026の方法。
[本発明1028]
前記生体サンプルが組織サンプルまたは血液サンプルである、本発明1027の方法。
[本発明1029]
前記がんががん療法に耐性である、本発明1001または1018の方法。
[本発明1030]
前記がんががん療法後に再発したものである、本発明1001または1018の方法。
[本発明1031]
前記がん療法が、化学療法、放射線療法、免疫療法、手術、ホルモン療法、幹細胞療法、標的療法、遺伝子療法、および精密療法(precision therapy)である、本発明1029または1030の方法。
[本発明1032]
a. がんを有する対象から生体サンプルを得る段階;
b. 該サンプルをアッセイし、GSK3αの阻害をもたらす変異を有するとしてがんを同定する段階; および
c. GSK3αの阻害をもたらす変異を有するがんを有するとして同定された対象に、アスパラギナーゼを投与する段階
を含む、がんを処置する方法。
[本発明1033]
a. GSK3αの阻害をもたらす変異を有するがんを有するとして対象を同定するアッセイ法の結果を受け取る段階; および
b. GSK3αの阻害をもたらす変異を有するがんを有するとして同定された対象に、アスパラギナーゼを投与する段階
を含む、がんを処置する方法。
[本発明1034]
前記がんが固形腫瘍である、本発明1032および1033の方法。
[本発明1035]
前記がんが結腸がんまたは膵臓がんである、本発明1032および1033の方法。
[本発明1036]
前記がんが転移性である、本発明1032および1033の方法。
[本発明1037]
前記生体サンプルが組織サンプルまたは血液サンプルである、本発明1032および1033の方法。
The singular "one (a)", "one (an)" and "the" include plural references unless the context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. Methods and materials similar to or equivalent to those described herein can be used in the practice or testing of the present disclosure, but suitable methods and materials are described below. The abbreviation "eg (eg)" is derived from the Latin word exempli gratia and is used herein to provide a non-limiting example. Therefore, the abbreviation "for example" is synonymous with the term "for example".
[Invention 1001]
A method for treating cancer that comprises the step of administering asparaginase and an agent that inhibits GSK3α to a subject with cancer.
[Invention 1002]
The method of the present invention 1001 wherein the cancer is selected from a list consisting of cancer, melanoma, sarcoma, myeloma, leukemia, and lymphoma.
[Invention 1003]
The method of the present invention 1001 in which the cancer is a solid tumor.
[Invention 1004]
The method of the present invention 1002, wherein the leukemias are acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL).
[Invention 1005]
The method of the present invention 1001 in which the cancer is resistant to asparaginase.
[Invention 1006]
The method of the present invention 1001 in which the cancer is not resistant to asparaginase.
[Invention 1007]
The asparaginase is selected from the group consisting of L-asparaginase (Elspar), pegaspargase (PEG-aspargase; Oncaspar), SC-PEG asparaginase (crowspargase pegol), and Erwinia asparaginase (erwinase). , The method of the present invention 1001.
[Invention 1008]
The method of the invention 1001 wherein the agent that inhibits GSK3α is selected from the group consisting of small molecules, antibodies, peptides, genome editing systems, antisense oligonucleotides, and RNAi.
[Invention 1009]
The small molecules are BRD0705, BRD4963, BRD1652, BRD3731, CHIR-98014, LY2090314, AZD1080, CHIR-99021 (CT99021) HCl, CHIR-99021 (CT99021), BIO-acetone oxime, SB216763, SB415286, abemaciclib (LY2835210), AT. Of the invention 1008 selected from the group consisting of -9283, RGB-286638, PHA-793887, AT-7519, AZD-5438, OTS-167, 9-ING-41, tideglusib (NP031112), and AR-A014418. Method.
[Invention 1010]
The method of the present invention 1008, wherein the small molecule is BRD0705.
[Invention 1011]
The method of the present invention 1008, wherein the RNAi is microRNA, siRNA, or shRNA.
[Invention 1012]
The method of the present invention 1001 in which inhibiting GSK3α is to inhibit the expression level and / or activity of GSK3α.
[Invention 1013]
The method of the invention 1012, wherein said expression level and / or activity of GSK3α is inhibited by at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or more as compared to a suitable control. ..
[Invention 1014]
The method of the present invention 1001 in which anti-cancer therapy has previously been performed on the subject.
[Invention 1015]
The method of the present invention 1001 in which anti-cancer therapy has not previously been performed on the subject.
[Invention 1016]
The method of any of 1001-1015 of the present invention, further comprising the step of diagnosing the subject as having cancer prior to the step of administration.
[Invention 1017]
The method of any of 1001-1015 of the present invention, further comprising receiving a result from an assay that diagnoses a subject as having cancer prior to the stage of administration.
[Invention 1018]
A method for treating cancer, comprising the step of administering asparaginase to a subject having cancer containing a mutation that results in inhibition of GSK3α.
[Invention 1019]
The method of the present invention 1018, wherein the mutation results in activation of the WNT signaling pathway in cancer cells.
[Invention 1020]
The mutations are R-spondin 1 (RSPO1), R-spondin 2 (RSPO2), R-spondin 3 (RSPO3), R-spondin 4 (RSPO4), ringfinger protein 43 (RNF43), and glycogen synthase kinase 3α ( The method of the present invention 1018, which is present in a gene selected from the group consisting of GSK3A, more commonly referred to as GSK3α).
[Invention 1021]
The mutations are R-spondin 1 (RSPO1), R-spondin 2 (RSPO2), R-spondin 3 (RSPO3), R-spondin 4 (RSPO4), ringfinger protein 43 (RNF43), and glycogen synthase kinase 3α ( The method of the invention 1018, which alters the expression of a gene selected from the group consisting of GSK3A, more commonly referred to as GSK3α).
[Invention 1022]
The method of the invention 1018, wherein the cancer is selected from a list consisting of cancer, melanoma, sarcoma, myeloma, leukemia, or lymphoma.
[Invention 1023]
The method of the present invention 1018, wherein the cancer is a solid tumor.
[1024 of the present invention]
The method of the present invention 1018, wherein the cancer is colon cancer or pancreatic cancer.
[Invention 1025]
The method of the present invention 1018, wherein the cancer is metastatic.
[Invention 1026]
The method of the invention 1018, wherein prior to administration, the subject is identified as having a cancer containing a mutation that results in inhibition of GSK3α.
[Invention 1027]
The method of the invention 1026, wherein the mutation is identified in a biological sample obtained from the subject.
[Invention 1028]
The method of the present invention 1027, wherein the biological sample is a tissue sample or a blood sample.
[Invention 1029]
The method of the present invention 1001 or 1018, wherein the cancer is resistant to cancer therapy.
[Invention 1030]
The method of the present invention 1001 or 1018, wherein the cancer has recurred after cancer therapy.
[Invention 1031]
The method of the invention 1029 or 1030, wherein the cancer therapies are chemotherapy, radiotherapy, immunotherapy, surgery, hormone therapy, stem cell therapy, targeted therapy, gene therapy, and precision therapy.
[Invention 1032]
The stage of obtaining a biological sample from a subject with cancer;
b. The step of assaying the sample and identifying the cancer as having a mutation that results in inhibition of GSK3α; and
c. The step of administering asparaginase to a subject identified as having a cancer with a mutation that results in inhibition of GSK3α
How to treat cancer, including.
[Invention 1033]
At the stage of receiving the results of an assay that identifies the subject as having cancer with a mutation that results in inhibition of GSK3α;
b. The step of administering asparaginase to a subject identified as having a cancer with a mutation that results in inhibition of GSK3α
How to treat cancer, including.
[Invention 1034]
The method of the present invention 1032 and 1033, wherein the cancer is a solid tumor.
[Invention 1035]
The method of the present invention 1032 and 1033, wherein the cancer is colon cancer or pancreatic cancer.
[Invention 1036]
The method of the present invention 1032 and 1033, wherein the cancer is metastatic.
[Invention 1037]
The method of the present invention 1032 and 1033, wherein the biological sample is a tissue sample or a blood sample.
Claims (38)
b. 該サンプルをアッセイし、GSK3αの阻害をもたらす変異を有するとしてがんを同定する段階; および
c. GSK3αの阻害をもたらす変異を有するがんを有するとして同定された対象に、アスパラギナーゼを投与する段階
を含む、がんを処置する方法に使用するための薬学的組成物であって、
アスパラギナーゼを含む、薬学的組成物。 The stage of obtaining a biological sample from a subject with cancer;
b. The step of assaying the sample and identifying the cancer as having a mutation that results in inhibition of GSK3α; and
c. A pharmaceutical composition for use in a method of treating cancer, comprising the step of administering asparaginase to a subject identified as having a cancer with a mutation that results in inhibition of GSK3α.
A pharmaceutical composition comprising asparaginase .
b. GSK3αの阻害をもたらす変異を有するがんを有するとして同定された対象に、アスパラギナーゼを投与する段階
を含む、がんを処置する方法に使用するための薬学的組成物であって、
アスパラギナーゼを含む、薬学的組成物。 At the stage of receiving the results of an assay that identifies the subject as having cancer with a mutation that results in inhibition of GSK3α;
b. A pharmaceutical composition for use in a method of treating cancer, comprising the step of administering asparaginase to a subject identified as having a cancer with a mutation that results in inhibition of GSK3α.
A pharmaceutical composition comprising asparaginase .
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
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| US201862697053P | 2018-07-12 | 2018-07-12 | |
| US62/697,053 | 2018-07-12 | ||
| US201862751129P | 2018-10-26 | 2018-10-26 | |
| US62/751,129 | 2018-10-26 | ||
| US201962839912P | 2019-04-29 | 2019-04-29 | |
| US62/839,912 | 2019-04-29 | ||
| PCT/US2019/041555 WO2020014581A1 (en) | 2018-07-12 | 2019-07-12 | Method for treating cancer |
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| JP2021530485A JP2021530485A (en) | 2021-11-11 |
| JPWO2020014581A5 true JPWO2020014581A5 (en) | 2022-07-20 |
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| US (1) | US20210299233A1 (en) |
| EP (1) | EP3820461A4 (en) |
| JP (1) | JP2021530485A (en) |
| CN (1) | CN112672739A (en) |
| WO (1) | WO2020014581A1 (en) |
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| BR102018001033A2 (en) * | 2018-01-18 | 2019-07-30 | Fundação Oswaldo Cruz | ASPARAGINASE ACTIVITY POLYPEPTIDE, EXPRESSION CASSETTE, EXPRESSION VECTOR, HOST CELL, PHARMACEUTICAL COMPOSITION, METHODS FOR PRODUCING AN ASPARAGINASE ACTIVITY AND FOR PREVENTING OR TREATING, AND CANCERING, CANCER. |
| WO2022063226A1 (en) * | 2020-09-24 | 2022-03-31 | 广州辑因医疗科技有限公司 | Use of compound for improving transplantation efficiency of human hematopoietic stem cells |
| WO2022211829A1 (en) * | 2021-03-30 | 2022-10-06 | Jazz Pharmaceuticals Ireland Ltd. | Dosing of recombinant l-asparaginase |
| CN114569616B (en) * | 2022-04-08 | 2023-05-02 | 武汉科技大学 | Small molecule composition and application thereof in preparation of medicine for treating neuroblastoma |
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| US20090004173A1 (en) * | 2004-05-28 | 2009-01-01 | St. Jude Children's Research Hospital | Diagnosis and Treatment of Drug Resistant Leukemia |
| GB0418328D0 (en) * | 2004-08-17 | 2004-09-22 | Imp College Innovations Ltd | Cancer methods and medicaments |
| CN104302782A (en) * | 2012-02-28 | 2015-01-21 | 诺华股份有限公司 | Cancer patient selection for administration of wnt signaling inhibitors using rnf43 mutation status |
| US20160375006A1 (en) * | 2012-10-12 | 2016-12-29 | The Broad Institute, Inc. | Uses of paralog-selective inhibitors of gsk3 kinases |
| US9855268B2 (en) * | 2013-03-05 | 2018-01-02 | Merck Patent Gmbh | Triazolo[4,5-d]pyrimidine derivatives |
| US20160312207A1 (en) * | 2015-04-21 | 2016-10-27 | The Board Of Trustees Of The Leland Stanford Junior University | R-spondin antagonists and methods of treating cancer associated with aberrant activation of wnt signaling |
| JP6856657B2 (en) * | 2016-02-26 | 2021-04-07 | アジオス ファーマシューティカルズ， インコーポレイテッド | IDH1 inhibitors for the treatment of hematological malignancies and solid tumors |
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- 2019-06-12 US US17/258,693 patent/US20210299233A1/en active Pending
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