Could lab-grown patient derived tumours be the next step towards truly personalised cancer treatments?

Two fluorescent microscopy images of intestinal organoids growing in synthetic hydrogels. Credit: N. Gjorevski/EPFL

Personalised cancer treatment is a rapidly developing and exciting field, with the long term goal being the creation of an individual’s genetic or molecular map for the rapid development of a personalised treatment that effectively controls or eradicates the disease. Current personalised treatments target specific characteristics of disease but are not truly unique to each individual. For example, the drug imatinib (Gleevec) is only used to treat chronic myeloid leukaemia in patients with the BCR-ABL fusion gene, so the treatment hasn’t been developed and produced specifically for one individual, but rather a subset of the patient population.

At the moment, these treatments are prescribed after screening, with the patient being monitored over the course of the treatment. Often a treatment doesn’t work as well as expected so another is prescribed, monitored and evaluated. This trial and error method is costly and time consuming, ultimately meaning that it can take months or even years before the patient is on their optimum treatment.

A recent study published in the journal Science, from The Institute of Cancer Research and The Royal Marsden Hospital, London, has investigated lab-grown ‘mini-tumours’, or patient derived organoids (PDOs), for the testing and development of personalised medicines. The aim is for an individual’s tumour cells to be grown into a PDO which can be used to test various drugs and treatments, minimising the time between diagnosis and the implementation of an effective treatment regimen.

71 patients with metastatic colorectal and gastroesophageal cancers were selected, all of whom had taken part in clinical trials and received intensive therapy to allow for a direct comparison between PDOs and in vivo reactions. Biopsies of their metastases were taken and grown into PDOs on a specialised gel, with an impressive 96% genetic similarity between the two. This is particularly important as new mutations and variations between the PDOs and the tumour’s genome can change the way cancer cells respond to treatment. Next, 55 different drugs were tested on the PDOs, ones that were either already licenced or in clinical trials, with the response measured and compared with the in vivo reactions from previous treatment regimens.

 

 

[The study] has the potential to help deliver truly personalised treatment and avoid the reliance on trial and error for many patients when clinicians give them a new cancer drug"

Dr Nicola Valeri, The Institute of Cancer Research, London

They found that if the PDO didn’t respond to treatment there was a 100% chance that the patient wouldn’t respond either. If the PDO did respond then there was an 88% chance that the patient would respond as well. Although this is slightly less reliable, there is still a nearly 9 in 10 chance of selecting a suitable treatment.

Notably, in one patient a genetic test indicated that their tumour would respond to a certain drug, yet the treatment failed in both the clinic and laboratory. This suggests that PDO testing should be used in conjunction with current diagnostic methods.  

Dr Nicola Valeri, from The Institute of Cancer Research in London, said "For the first time we proved these organoids not only resembled the biology of metastatic cancer, but also mirror what we see in the clinic. [The study] has the potential to help deliver truly personalised treatment and avoid the reliance on trial and error for many patients when clinicians give them a new cancer drug. "

This tool could spare the brutal side effects of drugs that may not even improve prognosis, opening up a new area of cancer diagnosis and treatment that addresses the difficulty in finding effective drugs, especially when the patient has already tried so many.

Previous attempts at treatment prediction involved growing the patient’s tumour inside a mouse model, testing different therapies on the mouse and analysing the results. This process, however, takes six to eight months for results to be generated, a prohibitively long period of time. This new approach aims to get results much more quickly, "With this tool we can get results in a couple of months and I think we can get even faster” said Dr Valeri.

 

 

This promising research moves us forward in the field of personalised medicine, and should ultimately lead to smarter, kinder and more effective treatments for patients"

Professor David Cunningham, the Royal Marsden NHS Foundation Trust

Ensuring that effective treatment is given at the earliest opportunity will slow tumour progression and improve prognosis, however, this research is still in its early stages with the study only analysing a small group of people with a particular subset of cancers. It’s not yet known how tumour cells from other cancers would respond to PDO generation and whether they would reliably indicate effective treatments.

This is still a very exciting study. Professor David Cunningham, from the Royal Marsden NHS Foundation Trust said "This promising research moves us forward in the field of personalised medicine, and should ultimately lead to smarter, kinder and more effective treatments for patients."