A class of cancer drugs known as KRAS inhibitors can shrink the painful nerve tumors that grow in people with neurofibromatosis type 1 (NF1), according to a study published Sept. 2 in the journal Science Advances. Researchers at Cincinnati Children's Hospital found that, in mice, the drugs worked at least as well as the MEK inhibitors that are already approved for the disease.
Why the tumors grow
NF1 is a genetic condition that affects about one in 3,000 people. About half of those with the disorder develop plexiform neurofibromas, non-cancerous tumors that form along nerves and can cause pain, disfigurement and, in some cases, turn malignant. The tumors appear when Schwann cells, which wrap around nerves, lose the NF1 gene. That loss switches on a protein called KRAS, which normally acts like an on-off switch for nerve growth.
Blocking the switch
The team, led by cancer biologist Nancy Ratner, studied mice engineered so their Schwann cells lacked the NF1 gene, the same type of model used in the research that led to MEK inhibitor drugs. When the mice were treated with KRAS inhibitors, the tumors shrank at rates that matched or beat the MEK drugs. "KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors," the authors wrote.
A faster path to patients
The finding matters because KRAS inhibitors are already in use or far along in development for certain cancers, which could speed up testing for NF1. MEK inhibitors such as selumetinib are approved for children with inoperable plexiform neurofibromas, but not every patient responds, and adults have fewer options. The researchers say the next step is to test KRAS inhibitors, possibly in combination with MEK drugs, in clinical trials for NF1 patients whose tumors keep growing.