Unraveling the secret of an aggressive cancer's response to treatment

Small cell lung cancer (SCLC) is a highly aggressive tumor that particularly affects heavy smokers.

Most patients undergo chemotherapy, which has a remarkable initial effectiveness in combating the tumor, due to its rapid spread. However, relapse often occurs over time.

Now, a team of scientists from the German University of Cologne, led by Professor Dr. Roman Thomas, Director of the Department of Translational Genomics and spokesman for the Collaborative Research Center 1399 (CRC 1399), has identified the mechanisms that govern the occurrence of relapse in the disease for the first time: The treatment is usually effective in the beginning due to The presence of predominant cancer cell populations that are sensitive to treatment at the time of diagnosis.

Scientists revealed that large clusters of sensitive cells hide many very different cancer cells. These cells usually arise from early precursors of the original cells, are resistant to treatment and can multiply unchecked after successful treatment.

Professor Julie George, lead author of the study, said: “Understanding the precise evolution of tumors in patients during treatment and relapse is a major challenge and an important goal. Our analysis reveals mechanisms that are likely to be relevant to many advanced cancers.”

For example, tumor recurrence (which occurs in almost all patients) usually reveals the presence of a different group of predominant cells. In additional treatments, such as radiation, the cancer cells showed characteristics of the genetic damage caused by the first chemotherapy.

Scientists have also discovered individual genetic characteristics in cancer cells, which are associated with a certain resistance to chemotherapy.

The study results show that the potential success of further therapeutic developments can always be limited by the large number of treatment-resistant cancer cells. Therefore, the most intensive initial treatment should be provided as much as possible in order to reduce the number of cancer cells, which may develop a certain resistance to treatment later.

Professor Roman Thomas said: “The results are quite realistic on the one hand, and provide hope for new treatment options in the future on the other hand.”

The study was published in the journal Nature.