Targeting lung cancer's Achilles heel
An EU-funded project has advanced lung cancer research by focusing on its weak spot - the epigenetic (or non-inherited) changes that differentiate cancer cells from healthy cells, making them prime targets for new therapies and earlier detection. The project results are already contributing to clinical trials and new screening tools.
Even when treated with a combination of chemotherapy, surgery and radiotherapy, survival rates for lung cancer, especially small cell lung cancer, are very low: on average only around 20% to 40% of patients diagnosed with Stage 2 lung cancers, at which point tumours are around 5cm in size, can expect to survive for five years or more with treatment.
Bringing together some of Europe’s leading specialists on genetics, epigenetics, pathology and oncology, the CURELUNG initiative has identified several epigenetic lung cancer biomarkers that could be potentially useful to target new therapies and early diagnosis.
The research is also contributing to the development of innovative tools to detect and characterise different types of lung cancer, and identify the most aggressive cancers in early-stage patients, as well as furthering clinical trials of new drugs.
“Not all cancers are the same, and not all patients will respond the same way to treatment. By identifying genetic alternations associated with specific cancer types we can create a list of biomarkers that can help determine the most effective, targeted treatment strategy for each individual patient while minimising the effect on healthy cells,” explains CURELUNG coordinator Manel Esteller, head of the Epigenetics and Cancer Biology Programme at Bellvitge Biomedical Research Institute (IDIBELL) in Spain.
Detecting cancer sooner
“One of the factors that makes lung cancer the most lethal type of cancer in the world is that it is usually diagnosed late, often after it has already metastasised and spread to other regions of the body. By identifying the biomarkers associated with lung cancer we can screen for them, allowing cancer to be detected and treated sooner, which should improve the effectiveness of therapies and increase survival rates,” Esteller says.
With that aim in mind, project partner MRC Holland, a biotech company, is building on work conducted in CURELUNG to develop screening tools for use in a clinical setting.
Equally important is determining the most effective course of treatment by identifying how drugs or combinations of drugs affect distinct forms of lung cancer brought on by different genetic alterations. In that regard, the biomarkers identified in CURELUNG are contributing to ongoing clinical trials in Germany run by pharmaceutical firms Novartis and AstraZeneca.
“The biomarkers we identified are being used by clinical researchers to determine if and how cancers with certain genetic alterations are affected by the drugs being tested, which should contribute to the development of new treatments for those cancer types,” the CURELUNG coordinator says.
With lung cancer accounting for 20% of all forms of cancer and causing the death of 1.6 million people worldwide each year – the most of any cancer – Esteller points out that if one drug is proven to be effective against 10% of lung cancers, and a second against another 10%, then the impact will only increase incrementally until a majority of lung cancers can be treated with targeted therapies.