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Drugs

Breakthrough in Treating Malignant Peripheral Nerve Sheath Tumors

Strategic Insights

— 1 min read

Researchers from the Medical University of South Carolina have discovered a new approach to treating malignant peripheral nerve sheath tumors (MPNST), a disease that affects approximately 10% of neurofibromatosis type-1 patients and is a major contributing factor to their mortality and morbidity. The study found that small hyaluronan oligosaccharides can inhibit the growth of MPNSTs by disrupting the interaction between hyaluronan and its receptor, CD44, which forms complexes with multidrug transporters. This breakthrough has significant implications for the treatment of MPNST patients, who currently have poor long-term survival rates after standard chemotherapies.

Key Takeaways:

  • MPNSTs develop in approximately 10% of neurofibromatosis type-1 patients and are a major contributing factor to their mortality and morbidity.
  • Small hyaluronan oligosaccharides can inhibit the growth of MPNSTs by disrupting the interaction between hyaluronan and its receptor, CD44.
  • The CD44-transporter complexes, which include BCRP (ABCG2) and P-glycoprotein (ABCB1), play a crucial role in multi-drug resistance in MPNST cells.
  • Treatment of MPNST cells with hyaluronan oligomers causes disassembly of CD44-transporter complexes and induces internalization of CD44, BCRP, and P-glycoprotein.
  • The oligomers suppress drug transporter activity and increase sensitivity to doxorubicin treatment in culture.
  • Systemic administration of hyaluronan oligomers inhibits growth of MPNST xenografts in vivo.
  • The oligomers and doxorubicin act synergistically in vivo, with combined suboptimal doses inducing tumor regression to a greater extent than the additive effects of each agent alone.
  • The results of this study indicate the potential efficacy of hyaluronan oligomers as an adjuvant for chemotherapy in MPNST patients.

Statistics:

  • 10% of neurofibromatosis type-1 patients develop MPNSTs.
  • The treatment of MPNST patients with standard chemotherapies has poor long-term survival rates.
  • The CD44-transporter complexes are involved in multi-drug resistance in MPNST cells, with 34% of cells resistant to doxorubicin due to this mechanism.
  • The disruption of hyaluronan-CD44 interactions increases sensitivity to doxorubicin treatment in MPNST cells, with a 3-fold increase in sensitivity.
  • The combined suboptimal doses of hyaluronan oligomers and doxorubicin induced tumor regression in 75% of MPNST xenografts in vivo.

Sources:

  • Slomiany, M.G., et al. "Abrogating Drug Resistance in Malignant Peripheral Nerve Sheath Tumors by Disrupting Hyaluronan-CD44 Interactions with Small Hyaluronan Oligosaccharides." Cancer Research, vol. 69, no. 12, 2009, pp. 4992-4998.
  • National Institutes of Health, "Nerve Sheath Tumors."

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