COMPOSITIONS AND METHODS FOR COMBATING DRUG-RESISTANT CANCERS

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

15/812,463

專利證號

US 10,413,564 B2

專利獲證名稱

COMPOSITIONS AND METHODS FOR COMBATING DRUG-RESISTANT CANCERS

專利所屬機關 (申請機關)

國立陽明大學

獲證日期

2019/09/17

技術說明

本研發成果主要是發現Cetuximab-resistant 的頭頸癌細胞，其Lymphotoxin-beta(LTb)都有高度表達的情形，並且會與EGFR有交互作用。EGFR-LTb interaction 會促進EGFR自體磷酸化，並讓其下游訊號傳遞活化，導致產生抗藥性。我們從結構生物學的角度切入，找出可能與EGFR交互作用的LTb beta-strand，並設計合成胜肽QDGLYYLYCLVGYR (P-5) (SEQ ID NO:5), WYTSVGFGGLVQLR (P-8) (SEQ ID NO:8), ERVYVNISH (P-9) (SEQ ID NO:9), 來阻擋破壞EGFR-LTb 交互作用，結果發現能有效抑制EGFR自體磷酸化，並抑制腫瘤細胞生長。 The present disclosure is based, at least in part, on the unexpected discovery that lymphotoxin- (LTb) mediates cetuximab resistance in cancer cells. LTb interacts with EGFR to enhance EGFR-ligand binding and to promote EGFR phosphorylation. Interception of EGFR-LTb interaction attenuates EGFR phosphorylation and reduces cetixumab resistance. Accordingly, one aspect of the present disclosure relates to a method for treating cancer in a subject, comprising administering to the subject an effective amount of an EGFR-interacting peptide comprising an amino acid sequence selected from the group consisting of QDGLYYLYCLVGYR (P-5) (SEQ ID NO:5), WYTSVGFGGLVQLR (P-8) (SEQ ID NO:8), ERVYVNISH (P-9) (SEQ ID NO:9), and a combination thereof, in which the cancer is resistant to cetuximab.

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