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1. (WO2017034234) COMPOSITE FORMULATION FOR TREATING CANCER HAVING HDAC INHIBITOR RESISTANCE
Latest bibliographic data on file with the International Bureau   

Pub. No.: WO/2017/034234 International Application No.: PCT/KR2016/009177
Publication Date: 02.03.2017 International Filing Date: 19.08.2016
IPC:
A61K 39/395 (2006.01) ,A61K 31/167 (2006.01) ,A61K 31/4045 (2006.01) ,A61K 38/07 (2006.01) ,A61K 48/00 (2006.01) ,C12Q 1/68 (2006.01)
[IPC code unknown for A61K 39/395][IPC code unknown for A61K 31/167][IPC code unknown for A61K 31/4045][IPC code unknown for A61K 38/07][IPC code unknown for A61K 48][IPC code unknown for C12Q 1/68]
Applicants:
서울대학교 산학협력단 SEOUL NATIONAL UNIVERSITY R & DB FOUNDATION [KR/KR]; 서울시 관악구 관악로 1 1, Gwanak-ro, Gwanak-gu, Seoul 08826, KR
Inventors:
이호영 LEE, Ho-Young; KR
Agent:
이명진 LEE, Myoung-Jin; KR
Priority Data:
10-2015-011770921.08.2015KR
10-2016-010475518.08.2016KR
Title (EN) COMPOSITE FORMULATION FOR TREATING CANCER HAVING HDAC INHIBITOR RESISTANCE
(FR) FORMULATION COMPOSITE POUR LE TRAITEMENT DU CANCER PRÉSENTANT UNE RÉSISTANCE À UN INHIBITEUR DE L'HISTONE DÉSACÉTYLASE
(KO) HDAC 억제제 내성을 갖는 암 치료용 복합제제
Abstract:
(EN) The present invention relates to a composite formulation for preventing or treating cancer having an HDAC inhibitor resistance, comprising an insulin-like growth factor 2 (IGF2) inhibitor and a histone deacetylase (HDAC) inhibitor as active ingredients. Also, the present invention relates to a method for predicting the reactivity of a cancer patient to an HDAC inhibitor, comprising the steps of (a) measuring the degree of methylation of an H19/IGF2 imprinting control region (ICR) in a cancer tissue sample, and (b) determining that the reactivity of the cancer patient to the HDAC inhibitor is low, in the case where methylation has been increased in the cancer tissue sample compared to a normal control group. The present invention can overcome the resistance of a histone deacetylase inhibitor through blocking of IGF2 or STAT3, and thus the present invention can be usefully used in a combination therapy of anticancer drugs based on the histone deacetylase inhibitor and can easily and effectively predict the anticancer drug resistance by a simple method of measuring methylation of the H19/IGF2 ICR.
(FR) La présente invention concerne une formulation composite permettant de prévenir ou de traiter un cancer présentant une résistance à un inhibiteur de l'histone désacétylase (HDAC), comprenant un inhibiteur du facteur de croissance insulinique de type 2 (IGF2) et un inhibiteur de la HDAC utilisés comme principes actifs. La présente invention concerne également une méthode permettant de prédire la réactivité d'un patient atteint d'un cancer à un inhibiteur de la HDAC, comprenant les étapes consistant à (a) mesurer le degré de méthylation d'une région de contrôle de l'empreinte (ICR) de H19/IGF2 dans un échantillon de tissu cancéreux, et à (b) déterminer que la réactivité du patient atteint d'un cancer contre l'inhibiteur de la HDAC est faible, dans le cas où la méthylation est plus élevée dans l'échantillon de tissu cancéreux par rapport à un groupe témoin normal. La présente invention permet de surmonter la résistance à un inhibiteur de l'histone désacétylase à travers le blocage de l'IGF2 ou du STAT3, et, par conséquent, la présente invention peut être utilisée de manière utile dans une polythérapie comprenant des médicaments anticancéreux basés sur l'inhibiteur de l'histone désacétylase et permet de prédire facilement et efficacement la résistance auxdits médicaments anticancéreux par un procédé simple de mesure de la méthylation de l'ICR de H19/IGF2.
(KO) 본 발명은, IGF2(Insulin-like growth factor 2) 억제제 및 HDAC(Histone deacetylase) 억제제를 유효성분으로 함유하는, HDAC 억제제 내성을 갖는 암의 예방 또는 치료용 복합제제에 관한 것이다. 또한, 본 발명은, (a) 암조직 샘플에서 H19/IGF2 ICR(imprinting control region) 부위의 메틸화 정도를 측정하는 단계, 및 (b) 정상대조군에 비하여 암조직 샘플에서 메틸화가 증가하였을 경우 HDAC 억제제에 대하여 암환자의 반응성이 낮은 것으로 판단하는 단계를 포함하는, HDAC 억제제에 대하여 암환자의 반응성을 예측하는 방법에 관한 것이다. 본 발명에 의하면, IGF2 또는 STAT3 차단을 통하여 히스톤 탈아세틸화효소 억제제의 내성을 극복할 수 있기 때문에, 히스톤 탈아세틸화 효소 억제제를 기반으로 하는 항암제의 병용 요법에 유용하게 이용될 수 있으며, H19/IGF2 각인 조절 부위(ICR)의 메틸화 측정이라는 간단한 방법으로 항암제 내성 여부를 쉽고 효과적으로 예측할 수 있다.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: Korean (KO)
Filing Language: Korean (KO)