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Is selumetinib the new ray of hope in neurofibromatosis??

Three genetically based illnesses that affect the nervous system are together referred to as neurofibromatosis. In this condition, tumors may develop anywhere in the neurological system, including the brain, spinal cord, and nerves., neurofibromatosis (NF) type 1, neurofibromatosis (NF) type 2 and Schwannomatosis (SWN) are the three types of neurofibromatosis. The symptoms vary depending on the type of NF. Cardinal signs of NF1 include light brown spots on the skin.(café lau ait spots) , freckles in the groin and armpits(Crowe’s sign), tiny bumps on the iris of the eye (lisch nodules), soft pea sized bumps or under the skin(neurofibromas),tumor on the optic nerve(optic nerve glioma),.. Hearing loss, early-onset cataracts, balance problems, flesh-colored skin flaps, and muscle atrophy are possible symptoms of NF2[1].

What is selumetinib?


Selumetinib, available under the trade name Koselugo® is a monoclonal antibody which comes under target therapy commonly used in cancers. Given orally, common side effects of this drug include vomiting, hair loss, constipation, nausea, stomach pain, dry skin, mouth ulcers, nose bleeding, loss of appetite, blurred vision, diarrhea, muscle ache, and redness around the finger nails.

What is the mechanism of action of selemetinib?

  • Selumetinib is a molecular targeted agent used in cancers. It works by stopping cell signals and pathways that help cancer cells to grow and expand.

  • In neurofibromatosis, it acts on the gene that is altering the production of neurofibromin,

  • a tumor suppressor protein which prevent this condition.

  • Apart from neurofibromatosis type I, it is also used in cancers like melanoma, glioma, and non-small cell lung cancers.

  • Severe adverse effects of this drug include cardiomyopathy, elevated creatinine phosphokinase, retinal vein occlusion, retinal pigment epithelial separation, and reduced vision.

  • Depending on how severe the adverse effects are, selumetinib should be withheld, the dosage decreased or completely stopped.

  • According to literature, about 24% of individuals experience severe adverse effects after consuming this drug, and 12% of those patients stop receiving treatment as a result of these effects.

  • It is also contraindicated in pregnant women and in patients who are having bleeding disorders due to the higher risk of bleeding.

When to use selumetinib in Neurofibromatosis?

The management of neurofibromatosis is mainly based on the relief of symptoms. The major concerns of treatment in this condition are the painful plexiform neurofibromas, benign peripheral sheath tumors that may turn into malignancy, malignant peripheral nerve sheath tumors that causes mortality, and optic nerve glioma. Treatment includes partial or complete excision of the tumor, and radiotherapy in order to make the tumor cells necrotic. Additionally in optic tumors, the usage of chemotherapeutic drugs like vincristine and carboplatin can be considered, but they have their own disadvantages like the development of resistance and side effects [2].

Treatment for plexiform neurofibromas has proven to be challenging. The tumors can increase rapidly in size and take up as much as 20% of a child's body weight. Because the tumors may be entangled with healthy nerves and tissue, surgery to remove the tumors is frequently not an option. In addition, tumors that have had partial surgical removal frequently come back, especially in young children. So alternate treatment options should be considered in treating them. According to the literature, molecular inhibitors that block several growth factors involved in the pathophysiology of neurofibromatosis have been tried[3].

The food and drug administration (FDA) granted selumetinib, available under the trade name koselugo® approval on April 10, 2020, for the treatment of young patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas. The patients must be at least two years old to use this drug. According to FDA, it should be taken twice daily, on an empty stomach, at a dose of 25 mg/m2.

It is the first treatment licensed for pediatric patients with this crippling and frequently disfiguring uncommon condition. This drug aids in slowing or halting tumor growth in neurofibromatosis by regulating the secretion of neurofibromin protein. Studies proved that plexiform neurofibromas, are completely diminished after treatment with selumetinib and children who received this drug reported less discomfort, better function, and overall improved quality of life. Since then, new drugs including cabozantinib, trametinib, binimetinib, and cobimetinib which has the same mechanism of action similar to selumetinib are also used in neurofibromatosis and hence have changed the way these tumors are treated[4].

No theory is valid unless practically proven

The main drawback of selumetinib is its action on the targeted genes in neurofibromatosis varies with the dose administered. In NF1 patients who do not have access to any other treatments, the use of selumetinib with remarkable anti-tumor activity may show long lasting therapeutic benefit. To identify the ideal age of administration, the length of the treatment, and the overall cost effectiveness of selumetinib, more research is necessary on long term safety and efficacy.


  1. S. Farschtschi, V.-F. Mautner, A. Cecilia Lawson McLean, A. Schulz, R. Friedrich, and S. K. Rosahl, “The Neurofibromatoses,” Dtsch Arztebl Int, vol. 117, no. 20, pp. 354–360, May 2020, doi: 10.3238/arztebl.2020.0354.

  2. J. Gachiani, D. Kim, A. Nelson, and D. Kline, “Surgical management of malignant peripheral nerve sheath tumors,” Neurosurg Focus, vol. 22, no. 6, p. E13, Jun. 2007.

  3. J. O. Blakeley and S. R. Plotkin, Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis,” Neuro Oncol, vol. 18, no. 5, pp. 624–638, May 2016, doi: 10.1093/neuonc/nov200.

  4. D. Casey et al., “FDA Approval Summary: Selumetinib for Plexiform Neurofibroma,Clin Cancer Res, vol. 27, no. 15, pp. 4142–4146, Aug. 2021, doi: 10.1158/1078-0432.CCR-20-5032.



IIT Guwahati
University of Manchester
Rhenix Lifesciences
American university of Sharjah
IIT Delhi
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