Important Publication: Impact of trametinib on the neuropsychological profile of NF1

Traditional clinical research for tumor treatments relied on objective and tumor-specific measures, for example decreased tumor size, as the outcomes to determine treatment success. While those measures are important, patients have reported that reducing side effects of tumor burden and size, such as a reduction in pain or an increase in balance, are also important benefits of treatment to consider. A recent publication in the Journal of Neuro-oncology has uncovered that treatment with a specific MEK inhibitor (trametinib) may have a positive impact on cognition in patients with NF1. While the results are preliminary and require further validation, their study showed an increase in processing speed, visuo-motor function, and verbal abilities for those patients on treatment with trametinib. This emphasizes the importance of researchers considering many outcomes, including psychological when designing clinical trials. Also, patient engagement in research to inform researchers about which factors are important to the patient is critical.

The first use of MEK inhibitors as a potential treatment for NF tumors came from early-stage discoveries by Children’s Tumor Foundation-funded researchers, who showed that MEK inhibitors could significantly affect NF tumor size. Collaborative efforts among the NCI, the NIH, the NFRP-CDMRP (Neurofibromatosis Research Program of the Congressionally Directed Medical Research Programs), NTAP (Neurofibromatosis Therapeutic Acceleration Program), and CTF ensured that this “MEK Story” proceeded expeditiously through proactive and strategic coordination, guaranteeing efficient use of donor/investor funding, and support from the federal government.

MEK inhibitors are a class (or group) of medications that have most often been used in melanoma (skin cancer) and other types of tumors. In the studies completed so far, MEK inhibitors have been shown to shrink tumors in the majority of people who take them. Why MEK Inhibitors in NF1? MEK is one of the components of the signaling pathway that is overactive in people born with NF1. It is the loss of NF1 and the activity of this pathway that is associated with tumor growth. The goal of MEK inhibitors is to block MEK signaling and therefore block the pathway.