At the beginning of drug treatment for non-small cell lung cancer, most tumors respond well to the medication. However, resistance to targeted therapy can develop during the course of treatment. DZL scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and the National Center for Tumor Diseases (NCT) in Heidelberg have now shown how the detection of tumor-specific DNA in the blood of many patients can detect the development of resistance even earlier than was previously possible with imaging methods.
Non-small cell lung cancer is the most common form of bronchial carcinoma, accounting for around 80 percent of all cases. Up to seven percent of non-small cell tumors are caused by a genetic rearrangement. The gene that contains the blueprint for the enzyme anaplastic lympohomkinase (ALK gene) is altered. The genetic rearrangement causes the ALK gene to be permanently activated and drives malignant tumor growth. In these cases, treatment with a so-called ALK inhibitor can slow down cancer growth. But sooner or later, resistance to the therapy develops. DZL scientists at the German Cancer Research Center and the National Center for Tumor Diseases (NCT) in Heidelberg are now showing how the detection of tumor-specific DNA in the blood of many patients can detect the development of resistance earlier than imaging methods.
"It is extremely important for patient survival to detect evidence of therapy resistance as early as possible. If the tumor continues to grow, the condition of the patients sometimes deteriorates rapidly," says DZL scientist Holger Sültmann from the DKFZ and NCT in Heidelberg. The disease is therefore monitored regularly to adjust the patients' treatment as soon as resistance emerges.
Detection of tumor DNA enables early identification of resistance
Sültmann and colleagues are working on using detection methods of tumor DNA in the patients' blood ("liquid biopsies") to detect a recurrence of the tumor as early as possible during therapy with ALK inhibitors. In the current study, the team examined a total of 343 blood samples taken from 43 patients at different time points during therapy with ALK inhibitors. The researchers combined two methods: targeted and very precise sequencing of individual genes associated with cancer recurrence (targeted next generation sequencing) and whole-genome sequencing.
ALK-related changes, indicative of tumor progression, were detected in 22 of the 43 patients. Many of the samples, taken at time points when the diseases were thought to still be held in check by therapy, already contained increasing amounts of tumor DNA. Overall, evidence of early disease progression was found in 19 of the 43 patients. In these cases, the detection of tumor DNA could have been used to examine the patients earlier using diagnostic imaging (CT).
Patients who had tumor-specific DNA detectable in their blood at the start of therapy had faster disease progression than those who had a negative result at the start of therapy. "The data show that the detection of tumor DNA in therapy monitoring of ALK-positive lung cancer could have a benefit for patients," says Holger Sültmann, adding, "However, these results still need to be confirmed in prospective studies."
Further information:
Original publication: Early identification of disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis.
Source: Tumor-DNA im Blut zeigt Fortschreiten von Lungenkrebs frühzeitig an
