Short peptide-based therapeutic agent and medicinal composition including the same for inhibiting activities of cancer cells

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

14/841,725

專利證號

US 9,802,998 B2

專利獲證名稱

Short peptide-based therapeutic agent and medicinal composition including the same for inhibiting activities of cancer cells

專利所屬機關 (申請機關)

國立成功大學

獲證日期

2017/10/31

技術說明

大多數癌症患者會直接化療或在進行切除手術之後接受化療。然而即使宣稱化療成功的患者仍然無法免於復發或後續抗藥性癌症的形成。再者，癌症復發的病人，尤其是化療過程中產生抗藥性的癌症患者，往往會因復發的癌細胞會轉移更快的現象而處於更高的危險性。已知實質固態瘤的周邊微環境充斥著發炎因子、白血球、血管過度增生及蛋白酶酵素，然而其形成原因及詳細機制仍有許多未明。先前我們發現癌細胞中CEBPD的減少有助於推動其進一步癌化，因此推論CEBPD表現的再活化可以抑制癌細胞的生長。最近我們的研究發現許多現行的抗癌小分子藥物 (如: Cisplatin (CDDP), Taxol 與 Fluorouracil (5-FU)) 均會活化癌細胞中的CEBPD表現；然而，我們也發現這些小分子藥物同樣也會活化巨噬細胞及纖維母細胞內CEBPD的表現增加。現在我們已經證實癌周邊組織細胞中CEBPD活化會促癌轉移的推論，並且其也可能可解釋化療過程中所產生的具抗性癌細胞，為何往往生長的更快並且更容易有轉移的情形發生。在實質固態瘤周邊的纖維母細胞及巨噬細胞中，我們已經找到一個新穎受CEBPD調控的分泌型因子 PTX3。最新的研究成果顯示，此一受CEBPD活化而誘導產生的PTX3具有促進血管新生及增加乳癌細胞、肺癌細胞及鼻咽癌細胞移行及侵入組織的能力。此些結果也指出PTX3可以成為一個癌症的治療標的基因，用以開發其抑制劑來應用於未來的癌症治療。 The majority of cancer patients receive chemotherapy directly or after surgical intervention. However, cancer patients are still at risk of recurrence or development of drug-resistant cancers. Patients with recurrent cancers, especially those with drug-resistant cancers during anticancer drug treatment, are always at a higher risk because these cancers spread faster than the original tumor. Recently, we found that CEBPD is responsive to many clinical chemotherapeutic agents. However, upon treatment with anticancer drugs, We further identified a novel CEBPD-regulated secretory factor, pentraxin 3 (PTX3), in cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM). We demonstrated that PTX3 was activated in response to CEBPD induction and promoted angiogenesis and the migration and invasion of cancer cells. These results indicated that PTX3 could be a therapeutic target for developing inhibitors to prevent the progression of cancers and drug-resistant cancers.

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