17th International Meeting of the European Society of Gynaecological Oncology (ESGO 2011) 11—14 September 2011, Milan, Italy
Targeted and combination therapies in ovarian cancer
Dr Cristiana Sessa – National Cancer Institute, Milan, Italy
We know that epithelial ovarian cancer is a broad disease and we know today that the different histotypes corresponded to different molecular dysregulations. Therefore we would be able to select the patients who have some particular molecular dysregulation and in those patients try to target the treatment and also to see if there’s an effect of the treatment. So to have both predictive biomarkers but also prognostic biomarkers which would be important.
Are there any other genetic markers?
The point is that BRCA is just one of the molecules which are dysregulated and which are under this umbrella of this homologous recombination repair system. And that’s quite an opportunity because this homologous recombination is very important in the repair of the damages which are induced by the drugs which are active in ovarian cancer. So it’s quite a unique situation for ovarian cancer. I think that it’s clear that there is already a compound which has been developed on the basis of this dysregulation and that’s a proof of concept, I mean PARP inhibitors. But in this line there will be other opportunities to use these PARP inhibitors, provided we could pick up the right patients.
Are PARP inhibitors used with success in ovarian cancer?
PARP inhibitors, yes, are mostly used in ovarian cancer; they are also used in breast cancer - triple negative breast cancer, in prostate cancer but tumour types it’s a bit more complicated because they are not tumours sensitive to platinum or where the DNA repair is so important. So I think in some ways triple negative breast cancer is in some ways similar but there are other variable factors which are important. In prostate cancer the consequence of the homologous recombination dysregulation is due to another upstream dysregulation and, therefore, it’s an indirect mechanism. So I think ovarian cancer could be the best example and application.
Are there other molecules you are checking for ovarian cancer?
Yes, I think that definitely while there are the antiangiogenics and I think that’s another point which is important because that corresponds to molecular alteration peculiar of ovarian cancer. Angiogenesis is important in ovarian cancer physiologically and so it was quite obvious to develop antiangiogenic compounds and they work. There are the PARP inhibitors or the drugs affecting the homologous recombination system which is a great variety of compounds. There are other new compounds like the anti IGFR receptor which are very promising in combination. So I think the point is that to identify the patients or the tumour type and then try to focus on that and then work pre-clinically to develop the optimal combination because per se this compound as single agent, they’re not so effective, we should add something with them. There is a lot of work on that and the point is that there is already a huge amount of information collected because that was collected prospectively which is important. So I assume that in a short run there will be indication on the biomarker and actually some of the presentation we had this morning alluded to, with the genetic profile which is important because all the other tools – microvessel density and so on – in the long run they didn’t prove to be adequate or to be efficient in that way.