Martin A. SCHWARTZ,P. Kumari ANDARAWEWA,Konstadinos MOISSOGLU
申请号：
US14785588
公开号：
US20160067314A1
申请日:
2014.04.18
申请国别(地区):
US
年份:
2016
代理人:
摘要：
Metastatic melanomas are highly resistant to radiation and chemotherapy from the earliest stages, which is a major factor in poor clinical outcomes. Activated leukocyte adhesion molecule (ALCAM)/CD166 was the gene that showed the highest correlation with detachment-induced chemoresistance. SiRNA-mediated depletion or antibody blocking of ALCAM specifically inhibited the increase in chemoresistance after detachment. This antibody also improved chemotherapeutic responses in a mouse xenograft model of human melanoma. Previous studies identified ALCAM as a marker for tumor aggressiveness and poor prognosis, and as a marker for “stemness”. Targeting ALCAM may therefore represent a novel approach for treatment of otherwise intractable melanomas. It was also found that stimulating integrin signaling enhanced chemosensitivity of melanoma to chemotherapeutic agents. The present invention provides a novel multimeric peptide construct comprising fibronectin fragments useful for stimulating integrin signaling and for enhancing chemosensitivity of melanomas.
