It is refreshing to come from one of the big meetings on cancer with optimism and faith in the future relevance of our translational research efforts. Too many bright bubbles surrounding "personalised medicine" have burst on subsequent tests of the underlying hypotheses. Last month’s ASCO meeting in Orlando was the usual bustle of gossip, educational snippets and bright bubbles, but one of those hasn’t burst. Two landmark studies focused on PARP inhibitors in women with bad prognosis advanced chemo/resistant breast cancer. The first was a smallish randomised trial (by O’Shaughnessy et al) of an intravenous PARP inhibitor named BSI/201, added, or not, to a conventional combination of gemcitabine and carboplatin in triple negative cancer patients. This shorthand term describes tumours which are negative for oestrogen, progesterone and Her2neu receptors and which are biologically aggressive and relatively chemoresistant. So no targets for "personalised medicine" approach, except a co/existence to BRCA mutations in maybe a third of cases.

The second trial (Tutt et al) reported a phase two non randomised study of an oral PARP inhibitor, olaparib, in patients with advanced chemoresistant breast cancers exhibiting just such mutations, either BRCA1 or 2. The bottom line is that the PARP targeted drugs added to response rates and survival in the first study, and achieved respectable numbers of responses in a third of the BRCA mutation bearing patients.

The good news is that there are several of these inhibitors on trial, as single agents, combined with DNA targeting drugs such as temozolomide, and also combined with radiotherapy. The not so good news is that the DNA repair inhibitory properties of the family are variably toxic to normal cells. This is particularly important as in the Milan Breast Cancer Conference this week, a vigorous debate is raging on the suitability of such agents in the chemoprevention of cancers linked to BRCA mutations. Overall good reasons for optimism, and brighter bubbles than usual!