Long chain fats and HER2

[R.B.]

This is very complicated.

It is more evidence that the long chain fats have a role in HER 2 BC. Exactly what role which fats and in what balance is the question

It seems to be saying that cutting of the long chain fat supply from the tumour has an inhibitory effect on herceptin resistance.

The question has to be which long chain fats produce resistance?

How and why are long chain fats contributing to resistance. Where in the fats pathways does herceptin work exactly? What does herceptin do in the fat pathways that inhibits BC?

Have they trialled for omega three and six as raw materials separately to see if they have a differential effect.

Can anybody explain the implications of super HER2 expression referred to in respect of resistance?


More questions than answers I'm afraid.


RB


1: Int J Oncol. 2007 Oct;31(4):769-76.
Pharmacological blockade of Fatty Acid Synthase (FASN) reverses acquired autoresistance to trastuzumab (Herceptintrade mark) by transcriptionally inhibiting 'HER2 super-expression' occurring in high-dose trastuzumab-conditioned SKBR3/Tzb100 breast cancer cells.
Vazquez-Martin A, Colomer R, Brunet J, Menendez JA.

Catalan Institute of Oncology (ICO)-Health Services Division of Catalonia; Girona Biomedical Research Institute (IdIBGi); and Department of Medical Oncology, Dr. Josep Trueta University Hospital of Girona, Girona 17007, Catalonia, Spain.


"We previously reported that pharmacological and RNA interference-induced inhibition of tumor-associated fatty acid synthase (FASN; Oncogenic antigen-519), a key metabolic enzyme catalyzing the synthesis of long-chain saturated fatty acids, drastically down-regulates HER2 expression in human breast cancer cells bearing HER2 gene amplification."


"Both HER2 mRNA and HER2 protein 'super-expression', which have not been reported in earlier Tzb-resistant breast cancer models, were entirely suppressed following pharmacological blockade of FASN activity."