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Preventive/remedy for cancer

A technology of preventive and therapeutic agents, applied in the field of cancer prevention or therapeutic agents

Inactive Publication Date: 2010-07-14
TAKEDA PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the link between trastuzumab-resistant cancers and signal transduction pathways has so far been unknown

Method used

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  • Preventive/remedy for cancer
  • Preventive/remedy for cancer
  • Preventive/remedy for cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1291]BT474 cells with high sensitivity to trastuzumab (American Type Culture Collection, HTB-20, J Natl Cancer Inst 61:967-978 (1978)), and BT-474 cells with low sensitivity to trastuzumab were used , the BT-474 cells with low sensitivity to trastuzumab were cultured for 3 months by culturing the BT474 cells with high sensitivity to trastuzumab in RPMI complete medium containing 5 μg / mL trastuzumab or longer. The LIMK1 gene was knocked down by the following RNAi method. Three kinds of Stealth RNAi corresponding to LIMK1 gene (LIMK1 Stealth Select 3 RNAi, Invitrogen Company, HSS140837: HSS140836: HSS141043) and LipofectaminRNAiMAX (Invtrogen Company, 13778-150) were in Opti-MEM(R)I reduced serum medium ( reduced-serum medium) (Invitrogen, 31985-070) to 36.7nMx3 (110nM in total) and 11μL / mL, respectively. After standing at room temperature for 20 minutes, the Stealth RNAi was mixed with each BT-474 cell suspension adjusted to 22,000 cells / mL in the culture medium at a liquid ...

Embodiment 2

[1294] BT474 cells with high sensitivity to trastuzumab (American Type Culture Collection, HTB-20, J Natl Cancer Inst 61:967-978 (1978)), and BT-474 cells with low sensitivity to trastuzumab were used , the BT-474 cells with low sensitivity to trastuzumab were cultured for 3 months by culturing the BT474 cells with high sensitivity to trastuzumab in RPMI complete medium containing 5 μg / mL trastuzumab or longer. The PAK1 gene was knocked down by the following RNAi method. Two kinds of Stealth RNAi (PAK1 Validated Stealth RNAi DuoPac, Invitrogen Company, 45-1676) and Lipofectamin RNAiMAX (Invtrogen Company, 13778-150) corresponding to the PAK 1 gene were in Opti-MEM(R)I reduced serum medium ( Invitrogen Company, 31985-070) were mixed to 55nM x2 (a total of 110nM) and 11μL / mL. After standing at room temperature for 20 minutes, the Stealth RNAi was mixed with each BT-474 cell suspension adjusted to 22,000 cells / mL in the culture medium at a liquid volume ratio of 1:11 (final con...

Embodiment 3

[1297] BT474 cells with high sensitivity to trastuzumab (American Type Culture Collection, HTB-20, J Natl Cancer Inst 61:967-978 (1978)), and BT-474 cells with low sensitivity to trastuzumab were used , the BT-474 cells with low sensitivity to trastuzumab were cultured for 3 months by culturing the BT474 cells with high sensitivity to trastuzumab in RPMI complete medium containing 5 μg / mL trastuzumab or longer. The cofilin 1 gene was knocked down by the following RNAi method. Three kinds of Stealth RNAi corresponding to cofilin 1 gene (CFL Stealth Select 3 RNAi, Invitrogen Company, HSS141559: HSS141560: HSS141561) and LipofectaminRNAiMAX (Invtrogen Company, 13778-150) were reduced in serum in Opti-MEM(R)I Mix in culture medium (Invitrogen, 31985-070) to 36.7nM x3 (total 110nM) and 11μL / mL. After standing at room temperature for 20 minutes, the Stealth RNAi was mixed with each BT-474 cell suspension adjusted to 22,000 cells / mL in the culture medium at a liquid volume ratio of...

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Abstract

It is intended to provide a preventive / remedy for trastuzumab-resistant cancer which comprises at least one drug selected from among a cofilin inhibitor, a PAK1 inhibitor, an LIMK inhibitor, an RHO inhibitor, a ROCK1 inhibitor and a ROCK2 inhibitor.

Description

technical field [0001] The present invention relates to a preventive or therapeutic agent for trastuzumab-resistant cancer, which comprises a cofilin inhibitor, a PAK1 inhibitor, a LIMK inhibitor, and a RHO inhibitor. More than one of , ROCK1 inhibitors and ROCK2 inhibitors. Background technique [0002] Currently, trastuzumab (trademark: herceptin), which is an existing HER2 inhibitor, has been widely used for HER2-expressing cancers. However, some cancers (even if they express HER2) are known to be non-responsive to trastuzumab, and even HER2-dependent cancers (for which trastuzumab is effective) develop adverse effects during their continuous treatment. Drug resistance to trastuzumab (non-patent document 1). As mechanisms for acquiring resistance to HER2 inhibitors, overexpression of MUC4, compensatory signaling through other HER families, compensatory signaling through the IGF-1 receptor, and through PTEN are known Changes in the downstream signaling pathway of / Akt (...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/7105A61K31/713A61K39/395A61K48/00A61P35/00A61P35/02A61P43/00
CPCA61K39/395A61K31/00C12N2310/14A61K31/7105C07K16/32A61K31/713C12N15/1137A61K45/06A61P35/00A61P35/02A61P43/00A61K2300/00
Inventor 大田义一林哲
Owner TAKEDA PHARMA CO LTD
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