[ASCRIT] Antisense chemoradioimmunotherapy consisting of anti-POEM (Arg-Gly-Asp) scFv linked onto high-energy radioisotopes, vinorelbine-tartrate and 21-nucleotide double-stranded siRNA targeted to DNMT1 induce apoptosis in metastatic breast cancer (MBC) characterized by hypermethylated p53, p16, RASSF1A, RAR-b2, BRCA2, H1C1, ESRI1, CDH1, Trbeta1, GSTP1, CCND2 and overexpression of bcl-2, cdc25c, Raf-1 and [alpha]8[beta]1 integrin

Author(s): J Giannios^1,3 , P Lambrinos² , E Maragudakis³ and N Alexandropoulos⁴

Introduction

Metastatic breast cancer (MBC) is resistant to almost all cytotoxic drugs and radiation, making it one of the most aggressive malignancies in humans, with the worst mortality. The failure of tumour cells to undergo apoptosis causes resistance to chemoradiological therapies due to overexpression of oncogenes and transcriptionally repressed apoptotic tumour suppressor genes due to aberrant methylation (CIMP⁺ ). Also, upregulation of the ECM gene POEM is associated with adhesion, migration and invasion of highly aggressive and MBC.

Materials and method

We obtained surgically a total of 168 MBC specimens from lymph nodes and lungs of patients. Genomic DNA of tumours was analyzed for CpG island hypermethylation...