Some mutations will be targetable, and some won’t be. In some cases, we may be able to interrupt the pathway, but in others we can’t.
—Michael Brada, MD, DSc
Peter Naredi, MD, European CanCer Organization (ECCO) Scientific Co-Chair of the Congress, stated in a press release: “In my view, Dr. Brastianos and colleagues very elegantly show what we mean with precision medicine, how genetic profiling can support our understanding of the metastatic process, and how it opens up different pathways for treatment. It is not enough to rely on the characteristics of the primary tumor, because brain metastases have other specific gene alterations, and in many patients, this gives us better treatment alternatives.” Dr. Naredi is Professor of Surgery at Sahlgrenska University Hospital, Gothenburg, Sweden.
Formal discussant of this study Michael Brada, MD, DSc, Professor of Radiation Oncology at the University of Liverpool, United Kingdom, who was not involved in this study, called the study “excellent.” He added: “This gives us a better understanding of the metastatic process.”
According to Dr. Brada, an important consideration from a clinical perspective is whether a metastasis is an early or late event in the lifetime of the primary tumor, because that may impact the success of therapy. It is possible that the current study could shed light on whether a metastasis is early or late, because the number of mutations observed is a function of time and can provide clues on the timeline of an individual metastasis. The data presented do not show whether these metastatic events were early or late.
Targetable vs Nontargetable Mutations
Due to the heterogeneity of cancer, “some mutations will be targetable, and some won’t be. In some cases, we may be able to interrupt the pathway, but in others we can’t,” Dr. Brada suggested. He said that it wasn’t possible from the data presented to tell whether metastases are heterogeneous or arise from a single dormant cell that lodges in the brain. “The answer may be a mixture of both,” he noted.
Even though targetable mutations were identified within the brain metastases, there are many challenges to overcome in attempting to use targeted therapy. “Those challenges include the existence of multiple targets within each cell, the enormous heterogeneity of the cells within the brain, and the heterogeneity of systemic diseases seen in the patients,” Dr. Brada continued.
“Certainly, this is an avenue to explore. Just because there is heterogeneity, doesn’t mean we shouldn’t be trying,” he added. ■
Disclosure: Drs. Naredi and Brada reported no potential conflicts of interest.
New research shows that paired primary tumor and brain metastases share a common ancestor, but as the metastases develop in the brain, they exhibit novel genetic alterations that can activate a number of signaling pathways. More than half of the mutations represent potential therapeutic targets....