Periodic Reporting for period 3 - CANCEREVO (Deciphering and predicting the evolution of cancer cell populations)
Período documentado: 2022-03-01 hasta 2023-08-31
Metastatic gastro-oesophageal cancers are incurable and are the third commonest cause of cancer death in the EU. Many of them become resistant to available treatments quickly but the cause of resistance remains largely unknown. These tumours demonstrate a high level of genetic instability which is thought to enable the evolution of drug resistance through Darwinian adaptation. We are developing new liquid biopsy technologies (called ‘whole exome circulating tumour DNA sequencing’ which only require a simple blood test) to identify how resistance evolves in detail and to develop methods that can predict resistance evolution.
So far, we established new liquid biopsy sequencing and computational methods to improve the sensitivity and specificity of these genetic analyses. We have also developed techniques to track evolution in blood samples and to make forecasts about the likely development of drug resistance even before patients have started a particular treatment. The approach is similar to making weather forecasts: we have shown that analysing basic genetic processes such as which mutations are most likely generated in an individual cancer and how they might undergo selection can be used to predict how long it will take for the tumour to develop resistance.
Demonstrating that such long-range forecasts are possible in principle is a major breakthrough. We will now test this in a larger cohort of gastro-oesophageal cancer patients who received different therapies, including chemotherapy, immunotherapy and targeted therapies. If we know which drugs are likely to stop working and when, it would help clinicians to select the treatment that works the longest and give them more time to plan for the next steps of the patient’s treatment. The new techniques that we are developing through this study will allow us to make predictions at the outset of a patient’s treatment and to stay a step ahead of the cancer.