How Searching for a Mutation Can Help Cancer Treatment

In In The News by Barbara Jacoby

From: European Society for Medical Oncology (ESMO)

Making the right therapeutic choice based on a tumour’s DNA

Individualised therapies that target the specific genetic features of tumours have the potential to transform cancer diagnosis, treatment and care.

Several challenges still need to be overcome before these approaches can be widely used in the clinic. Two DNA testing programmes have been implemented in institutes in Spain and the UK, to match patient tumour profiles with targets of early clinical trials, and to embed whole genome sequencing (WGS) in routine oncology practice, respectively. The results of these programmes, to be presented at MAP 2018, illustrate that new sequencing techniques and process restructuring at the system level can be the drivers of a model that promises new opportunities for the greatest number of patients.

Carmen Criscitiello of the European Institute of Oncology in Milan, Italy: “The evolution of sequencing techniques has allowed us to look for a wider array of mutations. For many of these, there is no registered drug available to target them. That’s why a key approach to implementing personalised medicine in the management of advanced-stage cancer is to develop clinical trials that show the effectiveness of drugs in cohorts of patients defined by the same genomic alteration.”

“As these trials target more and more distinct alterations in smaller and smaller populations, the main challenge now is patient accrual: with targeted mutations detectable in less than 10% of tumours, we need to screen huge numbers of individuals to find just a handful of people eligible for a trial. Managing the expectations of the many patients for whom analyses don’t lead to any meaningful treatment options is an issue that oncologists urgently need to address.”

However great the difficulties of putting all the pieces of the personalised medicine puzzle together, there is promise of a greater reward. Patients are already benefiting from the first tailored therapies that target their tumours’ genetic mutations: BRCA1 and BRCA2 genes, for example, are important for repairing the damage to DNA that occurs routinely throughout a cell’s life-cycle. Mutations of these genes within a cell can lead to DNA repair errors and ultimately to the cell’s death. In ovarian and breast cancers where such alterations are present, targeted drugs are used successfully to accelerate the death of tumour cells.

One major puzzle for oncologists – the prioritisation of multiple clinically relevant mutations in the same patient to inform therapeutic choices – was recently addressed with the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). ESCAT provides a classification of known tumour DNA mutations according to the level of clinical evidence supporting the use of specific drugs – registered or in development – to target them, which should simplify decision-making for oncologists and make treatments even more cost-effective.

MAP 2018 – Molecular Analysis for Personalised Therapy, a joint initiative of Cancer Research UK, UNICANCER and ESMO, brings medical oncologists, regulators and industry representatives together with the leading academic experts working in personalised medicine for cancer patients, to drive the investigation forward. The event taking place on 14-15 September in Paris, France, is a platform to present the latest and best evidence available in the field and unlock the secrets of making individualised treatment strategies work for more and more patients.