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New Findings Point to Need for ‘Double Whammy’ Drug Therapy for NF1 Malignancies

By October 23, 2009December 18th, 2023Awareness, NF1, Science & Research

Dr. Kim Hunter-Schaedle is working remotely today and has asked that I post her comments on these new findings:

New research suggests that a ‘double whammy’ approach of drug therapy may be the key to effectively treating the malignant tumors that can occur in NF1, and which often evade current therapies. The majority of NF1 tumors are benign (though it is important to emphasize that many, such as plexiform tumors, can become debilitating). However around 10% of persons with NF1 may, in their life, develop a malignant peripheral nerve sheath tumor (MPNST). These malignancies appear due to a molecular change in a formerly benign tumor; they are often first diagnosed because a patient reports pain in the tumor; but they have been a challenge for physicians to treat, and like all malignancies have the potential for rapid spread.

Understanding why a benign tumor becomes malignant is a keen area of focus in NF research, though it remains quite elusive.  Research published this week* in the Proceedings of the National Academy of Sciences suggests the key might be a dual attack on cell signaling pathways that are disrupted due to malfunction of two genes: NF1 and another tumor suppressor gene called PTEN.  The team figured this out by disrupting NF1 and PTEN gene activity at different times, in different tissues in mice called ‘conditional knockouts’. They found that when mice lacked the effective function of both NF1 and PTEN, all of the mice develop malignancies. Analysis of human MPNSTs showed NF1 to be inactive and PTEN to be inactive or operating at a reduced level or ‘dosage’ in the majority of malignant tumors.  These findings suggest that a progressive inactivation and shut down of PTEN activity could be a driving event as benign NF1 tumors become malignant, and that a combined blockade of NF1 and PTEN mediated signaling pathways could be a key to treating MPNSTs.

The reporting team is from University of California, San Francisco and collaborators including recipient of the Children’s Tumor Foundation 2009 Friedrich von Recklinghausen Award, Dr. Luis Parada (University of Texas Southwestern).

Gregorian Cet al. (2009) PTEN dosage is essential for neurofibroma development and malignant transformation. Proc Natl Acad Sci U S A. 2009 Oct 21. [Epub ahead of print]