Novel gene abnormalities discovered in a subpopulation of lung tumors could potentially identify patients with a good chance of responding to highly specific “targeted” drugs already in use for treating other cancers, according to a new study published in the journal Nature Medicine.
The genetic alterations—pieces of two genes fused together—showed up in a massive search of the DNA in stored tumor samples of non-small cell lung cancer. These specific genetic abnormalities had not been previously linked to the this cancer type.
Other cancers with similar genetic alterations often respond to “targeted” drugs that block overactive proteins called tyrosine kinase inhibitors. This suggests that the same drugs also may be effective against lung tumors driven by the newly found gene fusions. Because these drugs are already approved to treat cancer, it should be possible to move rapidly to clinical trials in lung cancer, the authors said.
If the trials are successful, physicians could potentially test patients’ tumors for the presence of the gene fusions and prescribe a medication matched to those alterations
“This is a textbook example of personalized medicine for lung cancer—a genetic alteration found in a subset of patients that we can now look for and use as a means to select particular therapies,” said Pasi A. Jänne, MD, PhD, a thoracic oncologist at Dana-Farber Cancer Institute and co-author of the study.
“In the past, although these targeted drugs were available, they were not chosen for a particular subset, but instead given to everybody,” he explained. “This will increase the likelihood of those therapies being more successful.”
The researchers estimate that less than 1% of Caucasians and about 2% of Asians with lung cancers carry this alteration—a fusion gene labeled KIF5B-RET. However, they said the finding opens a significant therapeutic opportunity.
“In a common indication like non-small cell lung cancer, identifying even a small subpopulation of individuals with gene fusions who may be responsive to a targeted therapy has the potential for major therapeutic impact,” said Philip J. Stephens, PhD, co-author of the study and executive director of cancer genomics at Foundation Medicine Inc. “This joint research with Dana-Farber translates genomic research to the clinic and we expect that it may quickly have a positive impact for patients."
Source: Dana-Farber Cancer Institute