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Nov 04, 2010
 |  BC Innovations  |  Cover Story

LAMbasting brain cancer

Approved therapies to treat brain cancer are not entirely tumor cell-specific and thus can have severe dose-limiting toxicities that decrease their effectiveness. A team of U.S. and German researchers thinks it has overcome this problem with a nanoconjugate that selectively targets brain tumor cells to block production of laminin-411-a proangiogenic protein that is highly expressed in cancerous but not normal brain cells.1Arrogene Nanotechnology Inc., which already has similar nanotechnologies in preclinical development to treat cancer, has in-licensed the findings.

Laminins are a large class of trimeric extracellular matrix proteins that play roles in angiogenesis, cell adhesion and migration, and other processes in both normal and cancer cells.A team co-led by Julia Ljubimova, professor of neurosurgery and director of drug development and nanomedicine in the Department of Neurosurgery at Cedars-Sinai Medical Center, previously showed that laminin-411 was overexpressed in 75% of glioblastoma multiforme (GBM) tumors compared with in normal brain tissues.2

In addition, the protein was associated with greater invasiveness and recurrence of GBM tumors.3 Collectively, Ljubimova said, the findings led her team to hypothesize that inhibiting laminin-411 could treat GBM.

Laminin-411 is composed of three subunits: laminin a4 (LAMA4), laminin b1 (LAMB1) and laminin g1 (LAMC1). The trimeric nature of laminins means that "you need to block the synthesis of at least two of the protein units in order to effectively inhibit laminin production," a difficult task for a single drug compound, Ljubimova told SciBX.

Thus the researchers set out to develop a nanotechnology capable of delivering two laminin protein inhibitors specifically to tumor cells.

The resulting nanoconjugate consisted of a...

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