New Breakthroughs in MPNST

Malignant peripheral nerve sheath tumor (MPNST) is a rare but very aggressive type of “sarcoma” tumor that develops from tissues surrounding nerves. Unfortunately, MPNST is only minimally sensitive to chemotherapy and radiation and most MPNST patients have only a 30 – 50% chance of surviving five years after their diagnosis. Researchers cannot develop new and effective therapeutic approaches for this deadly cancer because there is a lack of understanding of what genes or proteins have gone haywire to initiate the uncontrolled cell growth or cancer. Just two years ago, the Hope Fund for Sarcoma Research at NFCR began funding Dr. Dina Lev, a leading sarcoma researcher at M.D. Anderson Cancer Center in Houston, Texas (MDACC). Her laboratory has recently published two important papers on their contributions and discoveries to MPNST research that have far-reaching consequences for MPNST patients, providing them hope for development of new and effective treatments.

The first paper by the Lev team describes their development of a unique clinical and biological resource that will help physicians determine what the outcome will be for their MPNST patients. Until Dr. Lev’s important research, there was no adequate classification system for physicians to accurately stage or predict the outcome for their MPNST patients. Nor could physicians tailor treatments to benefit the individual patient’s needs. To fill this urgent need for patients with this rare and deadly tumor, the Lev team assembled a clinical database from the medical history, tumor size, surgical outcome, among other variables, of former MPNST patients treated at MDACC in the last 15 years. The team next created a tissue microarray (or a collection of tumor samples) from preserved tumor biopsies of many of the former MDACC MPNST patients and also from those of current patients. Using antibodies on the tissue microarray, the researchers detected abnormal protein mediators and molecular markers of MPNST. Importantly, because the microarray is directly linked to the clinical database, this combined resource is the first of its kind that allows identification of molecular biomarkers associated with the outcome for MPNST patients. The database will assist MDACC physicians and those elsewhere in determining the outcome for their MPNST patients. Moreover, it establishes the groundwork for an even larger and more accurate staging system as other data is added.

With the unique clinical database and tissue microarray completed, the Lev team quickly began using it for its other purpose—to identify potential therapeutic targets that may lead to better treatment strategies. The Lev team’s second paper demonstrates the expression, for the first time in MPNST tumor samples, of two proteins that mediate uncontrolled cell growth. Both proteins are related to the cancerous Ras protein – one of the few known abnormal molecules associated with MPNST. Continuing the experiments in live MPNST cell lines, the researchers impressively used a novel drug combined with standard drugs to block activity of both of the Ras proteins and inhibit cell line growth. Taken together, Dr. Lev suggests the inhibition of both of the Ras-related proteins with the combined agents is a potential effective therapy for MPNST patients. These published findings now serve as a guide for the MPNST research community to further develop and refine this treatment strategy, giving MPNST patients the hope they deserve to fight their cancer.

In summary, these investigations by Dr. Dina Lev have elucidated therapeutic targets that potentially could lead to novel and effective treatment strategies for patients suffering from MPNST, which provides new hope for MPNST patients.