Meaningful data on genetic alterations in tumors provide the basis for successful targeted therapy.
The teams led by Prof. Dr. Albrecht Stenzinger, Institute of Pathology, and Prof. Dr. Michael Thomas, Thoraxklinik at Heidelberg University Hospital, analyzed tissue samples taken from 3,000 patients with lung cancer during a study using combined DNA/RNA analytics. This diagnostic approach, which goes far beyond current international diagnostic standards and guidelines, helped them detect high-risk patients at an early stage, improve treatment, and gain information on new therapeutic approaches. The analysis of mutation and gene fusion is based on next-generation sequencing (NGS) (analyzing millions of DNA and RNA fragments at the same time) and only requires minimum amounts of tissue. This is the world’s largest study on combined genetic DNA and RNA analysis in routine diagnostics of non-small-cell lung carcinoma (NSCLC), which has recently been published in the “International Journal of Cancer”.
New targeted cancer therapies, which are drugs targeted against the characteristics of cancer cells resulting in the blocking of their growth, are developing rapidly. This increases the demands placed on molecular diagnostics, which provides important data for patient-specific treatment. “Targeted therapies can only be successful if they are tailored to the individual patient’s tumor,” says Prof. Albrecht Stenzinger from the Center of Molecular Pathology. “We will experience similar developments in the near future also in the field of immuno-oncology.” Here the drugs do not attack the tumor itself but activate the immune system to fight the cancer cells.
In the Heidelberg-based study, 3,000 patients with advanced non-small-cell lung carcinoma (NSCLC stages IIIb and IV) were examined using next-generation sequencing (NSG). On the one hand, the analysis included DNA regions promoting tumor growth and considered to be a starting point of various targeted therapies (e.g. EGFR, BRAF), or containing biomarkers with improved prognostic and predictive capabilities also for immunotherapies. On the other hand, gene fusions were analyzed using RNA sequencing. Gene fusions are alterations that promote tumor growth and are currently the target of therapies with tyrosine kinase inhibitors. “Contrary to conventional diagnostic procedures, the analysis of gene fusions on the RNA level is more sensitive and precise, as it allows us to identify the actually transcribed genes, which are the ones that are really active in the patient,” says. Prof. Stenzinger. This also makes it possible to identify high-risk groups.
The combined DNA/RNA analysis can be carried out in routine diagnostics with minimum amounts of tissue. “With a more targeted choice of treatment, the response rate to therapy as well as the time without disease progression can at least be increased threefold in patients with lung carcinoma when compared to chemotherapy,” says Prof. Dr. Michael Thomas from the Thoraxklinik.
Lung cancer is among the most common causes of death from cancer worldwide, with 80–85% accounting for the non-small-cell lung carcinoma (NSCLC) type. At an advanced stage, life expectancy is below 1.5 years despite chemotherapy. Some patients benefit from the development of tyrosine kinase inhibitors, while others respond to approaches from immuno-oncology, such as checkpoint inhibitors. There is an urgent need of further therapeutic approaches to improve the life expectancy of all patients.
“Our analysis allows for a deep insight into the molecular basics of the different conditions. This helps us make a better choice of treatment on the one hand and develop new translational approaches for the future on the other hand,” says Prof. Dr. Thomas.