Small cell lung cancer (SCLC) is a highly aggressive lung tumor that occurs particularly in heavy smokers. Because of the rapid spread of this type of tumor, most patients can be treated with chemotherapy alone with remarkable initial antitumor efficacy. However, relapse often occurs over time.
A research team at the University of Cologne led by Professor Dr Roman Thomas, director of the Department of Translational Genomics and speaker of the Collaborative Research Center 1399 (CRC 1399, Mechanisms of Drug Sensitivity and Resistance in Small Cell Lung Cancer), has now identified the mechanisms that govern this phenomenon for the first time: Because of the dominant populations of cancer cells sensitive to treatment at the time of diagnosis, treatment is usually effective at first. In addition, the team shows that these large sensitive cell populations harbor other numerous and highly diverse cancer cells. These cells usually come from early precursors of the original cells, are resistant to treatment and can proliferate uncontrollably after successful treatment. The study “Evolutionary Trajectories of Small Cell Lung Cancer under Therapy” was published in Nature.
Understanding development for targeted therapy
“It is a great challenge and an important goal to understand the exact growth of tumors in individual patients during treatment and relapse. Our analysis reveals mechanisms that are likely to be relevant in many advanced cancers,” said Professor Dr Julie George. lead author and co-speaker of CRC 1399;
For example, tumor regression – which occurs in almost all patients – usually revealed a different dominant cell population. In further treatments during treatment, for example with radiation, the cancer cells showed characteristics of the genetic damage caused by the first chemotherapy. In addition, the researchers were able to detect individual genetic characteristics in the cancer cells, which are associated with particular resistance to chemotherapy.
The study’s findings suggest that the potential success of further treatment developments could always be limited by the large number of treatment-resistant cancer cells. Therefore, a therapeutic approach would be to provide the most intensive initial treatment to minimize the number of cancer cells from which resistance may later develop.
We have taken a decisive step forward in understanding this disease and we very much hope that it will allow us to develop new treatment strategies that will lead to longer survival of affected patients. Although the results are somewhat discouraging on the one hand, they offer hope for new treatment options in the future on the other.”
Professor Dr. Roman Thomas
Source:
Journal Reference:
George, J., et al. (2024). Evolutionary trajectories of small cell lung cancer under treatment. Nature. doi.org/10.1038/s41586-024-07177-7.
