How research is paving the way for improved precision medicine to treat endocrine cancer

Precision medicine is an emerging medical approach where the management of disease is tailored according to the individual characteristics of each patient – essentially allowing medics to utilise targeted treatments to achieve the best outcomes.

Major technological advances in genomics have made it possible to identify critical genetic alterations in cancer, rendering oncology well along the path to precision medicine.

Tumours of the adrenal cortex – the outer part of the adrenal gland which produces hormones that are vital to life such as cortisol, which helps your body respond to stress – are, in general, among the most frequent type of abnormal and excessive growth of tissue in the general population with a prevalence of two to three per cent.

These tumours are mostly benign, but in rare cases they might be highly aggressive adrenocortical carcinomas (ACCs). Patients with these carcinomas present a generally poor prognosis with a total five-year survival rate below 40 per cent. However, the clinical outcome is sometimes variable even within a specific tumour stage, which makes patient consultation very difficult.

Recent developments in genetics, biochemical diagnosis and imaging techniques have set new standards for diagnosis and treatment of ACCs. Nevertheless, there is still no reliable classification in the clinical practice that can identify patients with higher risk of disease recurrence and progression.

In terms of treatment, surgery remains the only potential cure for patients with these types of carcinomas diagnosed at an early stage, while for advanced disease, standard pharmacological options show low response rates and many side effects.

Unfortunately, recent attempts to establish specific targeted therapies have been largely unsuccessful. However, in many of these patients, a fast bench-to-bedside transfer is highly needed, because many young patients in particular search desperately for new innovative treatment options after frequent failure of standard therapies.

In a recent study by University Hospital of Wuerzburg, Germany, and coordinated by myself, researchers investigated a large number of ACC samples on paraffin slides, which are easily available in the clinical setting.

The aim was to discover a ‘molecular signature’ that could be used to improve prognosis and to identify appropriate drugs to target the disease on a personalised basis.

This study demonstrated that using a combination of clinical, histopathological and molecular parameters may help to better predict the clinical outcome in ACC patients. In addition, at least one drug-targetable event was recognised in 60 per cent of samples, opening up new therapeutic opportunities for subsets of patients.

The results of this study represent a straightforward analysis that can be generally applicable in patient care and provide information simultaneously on an individual’s prognosis and potential targets for therapy. These data can be used for driving the clinical decisions in the management of individual patients with ACC, paving the way towards new precision treatment for individualised care.

The Institute of Metabolism and System Research at the University of Birmingham will now further develop this new approach and its potential application in the clinical practice of patients with ACC or other endocrine malignancies.

Dr Cristina L Ronchi
Clinician Scientist in Endocrine Oncology, Institute of Metabolism and Systems Research, University of Birmingham