What is Small Cell Lung Cancer

Small cell lung cancer: first molecular causes found - personalized therapy is approaching

It was a bit like looking for a needle in a haystack. The scientists looked for genetic changes in the lung cancer cells in millions of base pairs. "Without a highly specialized computer-aided evaluation on a high-performance computer and precisely fitting mathematical algorithms, this would not have been possible," says Dr. Martin Peifer. He carried out the study together with Prof. Dr. Roman Thomas at the University of Cologne. “We not only wanted to detect mutations in the genome of cancer cells, but also use statistical methods to assess their relevance for the development of the disease.” They were looking for genetic changes that drive tumor growth. After further characterization, such genes could form the basis for new, targeted therapeutic approaches - as alternatives to conventional chemotherapy.

Extremely many mutations

It is not uncommon for many years of heavy smoking to be the cause of lung cancer, small cell lung cancer, or SCLC for short small-cell lung cancer, is the most aggressive form of lung cancer. Once the diagnosis has been made, only about five percent of those affected will survive the next five years. Because even if the original tumor is still small, metastases can often already be found in other tissues or distant organs. Targeted therapies that specifically inhibit growth-promoting signaling pathways in cancer cells have not yet been available for this type of tumor. “Because targeted therapeutics can only be developed once the genetic changes that drive tumor growth are known. That is why, with the support of the Federal Ministry of Education and Research, we used innovative sequencing methods to search SCLC tumors for precisely these genetic changes, ”says Dr. Martin Peifer. The study found that small cell lung cancers have an extremely high mutation rate compared to other cancers. “We found an average of 7.4 protein-altering mutations per million base pairs. In other tumor types, such as ovarian tumors, only around 1.5 mutations per million base pairs are found, ”reports Dr. Peifer. “This mutation rate, which is much higher than that of many other types of tumors, is probably caused by carcinogens, i.e. carcinogenic substances. With small cell lung cancer, mostly through long years of heavy smoking. "

First targeted therapy approach

In detail, Dr. Peifer and his colleagues in the cancer cells gene changes that lead to the deactivation of the two tumor suppressor genes TP53 and RB1. When active, these tumor suppressor genes suppress and prevent the development of cancer. In 18 percent of the tumors examined, the researchers also detected genetic changes in the CREBBP and EP300 genes. "These mutations have a significant effect on histone modifications, which control the packaging and thus the accessibility and activity of the DNA," describes Dr. Peifer. Six percent of the tumors show an amplification, i.e. a duplication, of the gene for fibroblast growth factor 1, or FGFR1 for short. "We already found the gene amplification of FGFR1 in a previous study in 2010 in another subgroup of lung cancer, squamous cell carcinoma," explains Dr. Peifer. Doctors at the Center for Integrated Oncology (CIO) at the Cologne University Hospital are currently testing whether FGFR1 gene amplification actually allows a targeted therapeutic approach in a clinical study with the help of novel inhibitors in patients with squamous cell carcinoma of the lungs that carry this genetic change. Now that the scientists know that the genetic reproduction of the FGFR1 gene also plays a role in patients with small cell lung cancer, those affected with this tumor type were also included in the ongoing study.

Cologne researcher receives German Cancer Prize

For the discovery of these previously unknown genetic changes, among other things, Professor Thomas was recently awarded the German Cancer Prize 2013. With this award, the German Cancer Society honors the Cologne cancer researcher's achievements in translational cancer research. Translational research in medicine is about the early transfer of fundamental research knowledge into therapeutic application.

“We hope that our knowledge of the genes involved will enable us to better treat patients,” says Professor Thomas. "A determination of tumor-specific gene changes, which allows a personalized treatment of patients with lung cancer, is already in practice with us due to the close cooperation within the Network Genomic Medicine NGM at the CIO."

Contact Person:
Dr. Martin Peifer
Translational Genomics Department
University of Cologne
Weyertal 115b
50931 Cologne
Tel .: 0221 478-96863
Fax: 0221 478-97902
Email: [email protected]