Breast cancer: organoids offer personalised treatment even for the most challenging cases

The cells are taken. They are grown in an ideal environment – namely, a gel specifically designed to replicate the biological characteristics of the tumour, much like a real-life avatar. This creates a sort of ‘twin’ organ in which the tumour cells aggregate into small microspheres, coming together by the thousands to form translucent clusters. It is on these cell populations that the tumour – identical to the woman’s own – is studied to determine whether and to which drugs it responds. The scenario sounds like science fiction, but, although it needs to be tested on a large scale, it does not seem far removed from the reality of the near future. This is the outlook set out in a study published in *Cell Reports Medicine*, conducted by experts at the University of California, San Francisco, led by Jennifer M. Rosenbluth. The researchers have in fact developed this new method to predict the response to treatment of different types of breast cancer, using data from patients in a clinical trial (I-SPY2), combined with the results of rapid tests on mini-tumours grown in the laboratory.

The study analysed organoids from early-stage invasive tumours to investigate the mechanisms of resistance to treatment and thus pursue a precision medicine approach. By analysing specific response subtypes, a sort of ‘puzzle’ was created into which the predicted tumour responses to current therapies – such as chemotherapy, immunotherapy and targeted therapies – could be fitted. Finally, by drawing on data from actual patient observations and tumour marker results, these ‘response models’ were used to predict treatment responses in the organoids. The analysis focused in particular on triple-negative tumours, which are particularly aggressive (accounting for around 10–15 per cent of cases) and lack receptors for oestrogen, progesterone and the HER2 protein. This finding is of great importance because these women often have to undergo conventional chemotherapy (in combination with other treatments) even when resistance to treatment is observed.

By studying a particular tumour organoid – which exhibited the highest predicted and subsequently validated resistance to a combination of chemotherapy and a targeted drug – the research team then set out to analyse nearly 400 potential drugs that might be active against this organoid. The analysis made it possible to identify the optimal chemotherapy combination for this specific type of tumour, starting directly from the organoid. Drug screening on the organoids also revealed other promising results, including in terms of future targeted treatments for groups of patients. “It has been shown that breast tumour organoids express important tumour biomarkers, many of which can be targeted by drugs,” commented the first author, Tam Binh V. Bui, in a statement from the American university. “These organoids have enabled us to study the effects of drugs directly on human tissue and to prioritise the most promising therapies for this subtype.”

The research may pave the way for the development of more personalised treatments for breast cancer, including triple-negative breast cancer, which is particularly aggressive and difficult to treat. “Breast cancer organoids have replicated the response of patients’ tumours to therapies and identified potential combination therapies for tumours that do not respond to standard treatment,” says Jennifer M. Rosenbluth. “These findings support the use of organoid modelling as a bridge between clinical biomarkers and precision treatment strategies in breast cancer.” “Tumour organoids have been studied in oncology for around 15 years and represent a promising tool for understanding how a tumour might respond to drugs,” explains Lucia Del Mastro, Professor of Medical Oncology at the University of Genoa. This research is also particularly interesting for treatment-resistant triple-negative breast cancers: organoids obtained directly from the tumour cells of patients who had not responded to pre-operative treatment were evaluated to identify approaches capable of overcoming resistance to chemotherapy. “The use of organoids could therefore make treatment increasingly personalised and effective,” concludes the expert. However, some limitations remain: organoids do not fully replicate the actual tumour environment, particularly the immune system and the tissues surrounding the tumour, which in turn can influence the response to treatment. Therefore, these very promising results need to be confirmed in larger studies.”