But that could change due to a new, experimental procedure to kill metastatic breast cancer cells presented by John Giannios, MD, head of radiotherapeutic cancer research, IASO Hospital, Athens, Greece, at the 18th Annual Meeting of the European Association of Cancer Research in Innsbruck, Austria, on July 6, 2004. Giannios's
team looked for overexpression of known oncogenes in advanced breast cancer tumor tissue.They found overexpression of the oncogenes bcl-2, HER-2, Raf-1 and cdc25c, but also observed overexpression of DNMT1.DNMT1, a DNA methyltransferase, is involved in DNA replication during cell division, and is implicated in cancer development.The team also observed methylation of BRCA1 promoter, specifically implicated in the development of breast cancer tumors.
"What I have done is molecular targeted therapy circumventing chemoresistant and radioresistant mechanisms," says Giannios
.Dubbed "chemoradioimmunotherapy," the technique combines chemotherapy, radiation therapy, and immunotherapy.The chemotherapy aspect involved vinorelbine-tartrate.The radiotherapy aspect was the use of high energy radioisotopes.And the immunotherapy component consisted of attaching an HER-2 specific antibody to the radioisotopes, as well as the inclusion of a 21-nucleotide double-stranded siRNA (small interfering RNA) created against DNMT1.Giannios's
team hoped the treatment regimen would target the tumor cells by blocking the molecular mechanisms that protect the cells from conventional treatment.
"I am very optimistic about the results," says Giannios
.Within 24 hours of treatment there was evidence that the treated tumor cells were dying at a significantly higher rate than in the untreated control cells."Apoptosis was confirmed by the detection of activation of caspase-3-9, an enzyme involved in apoptosis, inhibition of DNA synthesis and metabolic activity in the tumor cells and the formation of apoptotic bodies.These apoptotic bodies were seen to be phagocytosed (absorbed) by adjacent tumor cells, which resulted in the subsequent apoptosis of the tumor cells through a "bystander" killing effect."
"What we hope to achieve is that this is going to circumvent conventional treatment and make treatment more specific.It's not like a blockbuster policy, like conventional chemotherapy," says Giannios