Internal enhancement of DNA damage by a novel bispecific antibody-drug conjugate-like therapeutics via blockage of mTOR and PD-L1 signal pathways in pancreatic cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a refractory malignant tumor with poor prognosis, limited chemotherapeutic efficacy, and only about 5% of 5-year survival rate. We generated a dual-targeting ligand-based lidamycin (DTLL) to investigate its efficacy against pancreatic cancer after preparing its precursor, DTLP. DTLP was shown specifically binding to EGFR and HER2 on cell surface, followed by endocytosis into cytoplasm of pancreatic cancer cells. DTLL significantly promoted apoptosis and cell cycle arrest at G2/M stages and inhibited cell proliferation. Pancreatic tumors of either MIA-paca-2 cell line-derived (CDX) or patient-derived xenograft (PDX) mouse models were significantly regressed in response to DTLL. It suggested that DTLL might be a highly potent bispecific antibody-dru

SUBMITTER: Cao R 

PROVIDER: S-EPMC6382721 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature