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THERAPEUTIC OR PROPHYLACTIC AGENT FOR CANCER

外国特許コード F140007849
整理番号 S2012-0310-C0
掲載日 2014年2月28日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2013JP050907
国際公開番号 WO 2013108869
国際出願日 平成25年1月18日(2013.1.18)
国際公開日 平成25年7月25日(2013.7.25)
優先権データ
  • 特願2012-009665 (2012.1.20) JP
  • 特願2012-009688 (2012.1.20) JP
発明の名称 (英語) THERAPEUTIC OR PROPHYLACTIC AGENT FOR CANCER
発明の概要(英語) Disclosed are: a novel means useful for the treatment and prevention of cancer; and a novel therapeutic/prophylactic means effective even for cancer that is resistant to anti-cancer agents. As a result of extensive studies, the inventors of the present application have identified ErbB2 as a cell membrane receptor for CCN2. A first therapeutic or prophylactic agent for cancer according to the present invention comprises a substance capable of inhibiting the interaction between CCN2 and ErbB2 (i.e., a CCN2-ErbB2 interaction inhibitor) as an active ingredient. A second therapeutic or prophylactic agent for cancer according to the present invention comprises a CCN2-ErbB2 interaction inhibitor as an active ingredient and is used in combination with an anti-cancer agent capable of inducing apoptosis.
従来技術、競合技術の概要(英語) BACKGROUND ART
ErbB2 (Also referred to as HER2.) Is, epidermal growth factor receptor (EGFR) family members to penetrate a cell membrane surface protein, 1 human breast cancer patient population of approximately one-half 5 is highly expressed is known. ErbB2 As a therapeutic target for treatment of cancer research and, as a therapeutic agent is an antibody or anti-ErbB2 cancer, ErbB2 binding to the extracellular region of the various known peptide sequences (such as Patent Document 1-5). For example, over-expression of ErbB2 was confirmed primary and metastatic breast cancer are put to practical use as a therapeutic Herceptin (trade name, generic name is trastuzumab) is, ErbB2 epitope of the extracellular region of the molecule (the first the first region of amino acids No. 529 - No. 625) that specifically binds to the anti-ErbB2 humanized monoclonal antibody (non-patent document 1) in a medicament.
In this way are studied in ErbB2, ErbB2 of the EGFR family is a member of one of orphan receptors 4 (also referred to as an orphan receptor.) And, the ligand is not reported yet. Patent Document 6 is, ligand binding to the receptor tyrosine kinases can be used for treatment of cancer is described, there is no disclosure relating to specific ligands of ErbB2.
CCN2 Is, connective tissue growth factor (connective tissue growth factor; CTGF) also known as a protein, belonging to the family CCN secretory growth-promoting factor. As the biological function of the CCN family, cell proliferation, differentiation, migration, adhesion and irritation or extracellular matrix formation, angiogenesis and tumor formation and involvement in (non-patent document 2, 4, 18). CCN2 Of the cell surface (non-patent document 5) aggrecan, fibronectin (non-patent document 6), integrin (non-patent document 6-10) can be combined, in cooperation with the matrix metalloprotease (non-patent document 13, 14), promote the expression of extracellular matrix proteins (non-patent document 11), as well as to modulate the activity of cell adhesion, also acts as the angiogenic factor is known (non-patent document 12). Generated in the course of the individual tissue formation in the cartilage tissue found in the strong expression of CCN2, CCN2 endochondral ossification is believed enhancer (non-patent document 15) are. Further, breast cancer, pancreatic cancer, melanoma, chondrosarcoma, in elevated expression of CCN2 and a number of fibrosis is confirmed (non-patent document 16). CCN2 Various roles in various cancers is the look, that overexpression of CCN2 in breast cancer cells increases in tumor size and metastasis and is considered to be related to the (non-patent document 16). In addition, the formation of osteolytic bone metastases in breast carcinoma CCN2 is deeply involved is shown (non-patent document 17).
CCN2 Is, (insulin-like growth factor binding protein-like) IGFBP domain, domain (von Willebrand factor type C) VWC, TSP1 repeat (thrombospondin type 1), 4 (C-terminus) domain CT one domain (non-patent document 2). These each of the domains is different from the binding partner. CCN2 Domain binding of integrin α 5 β 1 CT, promote cell adhesion and migration (non-patent document 9). In addition, both the domain and a fibronectin interact directly, via integrin α 5 β 1 promoting adhesion of chondrocytes (non-patent document 19). Further, said domain comprises integrin receptor α v β 3 C-terminus heparin binding domain and the direct binding and heparan sulfate proteoglycans and via direct conjugation, to induce the adhesion of the hepatocytes (non-patent document 20).
However, with regard to the relationship between the ErbB2 and CCN2 not reported No.
On the other hand, taxol is (trade name, common names are paclitaxel), taxane anti-cancer agent and a registration system, polymerization of the said tube Blinn - stabilizing microtubule formation by inhibiting cell division to prevent, inhibit the growth of cancer cells (non-patent document 21). Other various types of cancer of the breast and ovary taxol cancer used in the treatment and prophylaxis of, in this case Taxol-resistant cancer cells has been the emergence of a problem. Drug resistance and novel means useful in the treatment of cancer are also demanded.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • 発明者(英語)
  • TAKIGAWA, Masaharu
  • HATTORI, Takako
  • MINAGAWA, Sachi
  • SETO, Yasuhiro
  • TSUNA, Mika
  • HARADA, Yoshitaka
  • TAKAHISA, Manabu
  • YASUDA, Hideyo
国際特許分類(IPC)
指定国 National 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 IS KE KG KM KN KP KR KZ LA LC LK LR LS LT 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 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
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
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
OAPI: BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

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