COMPOSITIONS AND METHODS FOR INHIBITING CHEMORESISTANCE IN CANCER AND IMPROVING RESPONSE TO THERAPY
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.
申请公布号
WO2014172634(A1)
申请公布日期
2014.10.23
申请号
WO2014US34648
申请日期
2014.04.18
申请人
UNIVERSITY OF VIRGINIA PATENT FOUNDATION;SCHWARTZ, MARTIN A.;ANDARAWEWA, P. KUMARI;MOISSOGLU, KONSTADINOS
发明人
SCHWARTZ, MARTIN A.;ANDARAWEWA, P. KUMARI;MOISSOGLU, KONSTADINOS