Advancing personalised medicine
BRAF is a protein that plays an important part in the transmission of growth signals. In a mutated state it can lead to uncontrolled cell growth. Around every second malignant melanoma – the deadliest and most aggressive form of skin cancer – has a certain mutation of the BRAF gene.
As has now been shown, affected patients respond particularly well to the substance Vemurafenib. Their average lifespan is around 40% higher than with conventional chemotherapy, according to a current study presented at the Congress of the European Society for Medical Oncology (ESMO). This substance, recently licensed in the EU, is a fitting example for a treatment concept that has undergone rapid developments in recent years – personalised medicine. ‘The next ten to fifteen years will see us make real strides toward genuinely personalised treatment for cancer patients,’ said ESMO president Dr Martine Piccart, during the society’s 2012 meeting held recently in Vienna.
The right drug in the right dosage at the right time is, to coin a snappy slogan, the objective of individualised medicine. ‘Personalised medicine is about matching patients to the treatments that work best for them. In oncology, personalised medicine is becoming a clinical reality, with targeted treatments already in use,’ explained Professor Antanasio Pandiella, Translational Oncopharmacology Unit Director and Vice-director at Salamanca Cancer Research Centre in Spain. ‘The concept of one chemotherapy drug fits all is now history. We are increasingly defining treatments according to the molecular characteristics of individual tumours.’
Cancer develops through genetic mutations in the body’s cells. The genome of some types of tumour contains up to 100,000 changes of the genetic material. Not all of them are relevant to cancer development, with the number of ‘cancer-genes’ currently estimated at around 300 ¬¬– 400. During genetic tests carried out in the context of cancerous diseases only very few genetic mutations are classed as biomarkers. If Dr Pier Giuseppe Pelicci, CO-Scientific Director of the European Institute of Oncology (IEO) in Milan, Italy, had his way, whole genome testing will soon be part of clinical routine: ‘This could identify new prognostic markers and new therapeutic targets.’
‘Increasingly extensive sequence analyses of cancer genomes have led to the discovery of new mutated cancer genes and have explored the extant patterns of somatic mutation,’ explained Professor Michael Stratton, Director of the Wellcome Trust Sanger Institute in Cambridge (UK) and joint head of the Cancer Genome Project, which aims to elucidate the genetic causes of human cancers. In the context of the Cancer Genome Projects some catalogues of the mutations in the genome of individual breast cancers have already been compiled. ‘The combinations of mutated cancer genes and the mutational processes that are operative in the subclasses of breast cancer are becoming apparent,’ said Prof. Stratton, summarising the research results. During ESMO, other oncologists reported on the cartography of the genetic landscape for pancreatic cancer and melanoma.
Nonetheless, personalised medicine must also overcome some obstacles: ‘We are very concerned about the huge bureaucracy involved in running clinical trials,’ explained ESMO President Piccart. ‘We hope that the new clinical trials directive, due to come into force in 2016, will facilitate research.’ Another new directive in development also has a potentially important impact on clinical trials: the new Data Protection Regulation, currently in draft form. ‘In cancer research, we need to be able to share data,’ she added.
Dr Paolo G Casali, head of the Adult Sarcoma Medical Oncology Unit, Istituto Nazionale Tumori, Milan, Italy, refers to a methodological problem: The more individualised the treatment the more difficult the clinical examinations. ‘We need hundreds of patients for a clinical study. If the target groups become increasingly smaller we won’t be able to achieve these numbers,’ he warns. Concerning data protection and the clinical trials directive he cautioned, ‘There will be no personalised oncology at all if we don’t change the rules.
17.01.2013
