The biology of Langerhans cell histiocytosis (LCH) has been a mystery for decades, hampering the development of effective therapies. The biggest debate is centered around the nature of the disease. Is it an autoimmune disease? A cancerous condition? Or something else?
Recent studies revealed cancerous mutations in the LCH tumors of several patients. These mutations, in a gene called BRAF, are found in many other cancers. This discovery is nothing short of revolutionary because not only does it settle the debate on what LCH is, but also opens up new avenues for treatment.
We are engaged in two main research projects here at Cincinnati Children's:
- We have identified mutations in many other genes in patients who don’t have mutations in BRAF. These include genes, such as MAP2K1, which are in the same biologic pathway as BRAF. In the laboratory, we are investigating how these mutations lead to LCH, with the goal of developing safe, effective treatments.
- We are running clinical trials testing novel drugs specifically targeting BRAF. So far, the results look promising. We aim to determine the safety and efficacy of these new agents with the eventual goal that these drugs will become the main treatment for LCH rather than the current treatments, which can be toxic.
Dabrafenib: This study will help determine the safety, tolerability and pharmacokinetics of oral dabrafenib in pediatric subjects with advanced BRAF V600 mutation-positive solid tumors.
Trametinib: Study to investigate safety, pharmacokinetics, pharmacodynamics and clinical activity of trametinib in pediatric subjects with BRAF V600 mutations. Learn more.