Method of Using MeK Inhibitor to Prevent Radiation Induced Fibrosis

Thomas Jefferson University Background
Patients receiving radiation therapy are susceptible to fibrosis formation at or around the site of the targeted radiation exposure. One of the major contributors to morbidity via treatment is radiation-induced fibrosis (RIF), which may occur in the skin and subcutaneous tissue, lungs, gastrointestinal and genitourinary tracts, as well as any other organs in the treatment field. Radiation itself initiates cell and tissue injury leading to chronic inflammation and release of cytokines which ultimately stimulates trans-differentiation of fibroblasts into myofibroblasts. RIF causes excessive proliferation in this population which, in turn, produces excess collagen and other extracellular matrix (ECM) components, which alter tissue architecture and function drastically. Researchers at Thomas Jefferson University have identified that protocols and methods using trametinib as a prophylactic and long-term medication reduce the formation of the biomarkers corresponding to myofibroblast formation, and those effective therapeutic strategies employing the MEK1/2 inhibitor trametinib are effective for reducing or preventing the formation of fibrosis.
Technology Overview
Jefferson researchers determined the effect of the MEK1/2 inhibitor, trametinib, which is in clinical use in the treatment of malignant melanoma, on the TGF-β induced rat peritoneal mesothelial/mesenchymal transition (MMT) and abdominal adhesion formation in a mouse model. Trametinib effectively blocked the MMT in vitro and markedly diminished adhesion formation in vivo, likely by inhibiting the activation of Erk l/2, a mitogen-activated protein kinase pathway involved in cell proliferation. In addition, there was no impairment of the wound healing of the abdominal muscles and skin of the mice at the laparotomy site with the therapeutic doses of trametinib utilized. This method of providing trametinib may be able to both treat the fibrosis formation, by preventing or reducing the occurrence of fibrosis due to the radiation treatment, while also providing for a reduced radiation dose needed for the patient to treat and destroy the cancerous cells. These findings indicate that trametinib may be a useful drug for the inhibition of adhesion formation and warrant human clinical studies. This technology is available for licensing and other partnerships. 

A novel solution in preventing fibrosis at sites of radiation therapy in patients with cancer 
May reduce the radiation dose needed for treatment 

Available for licensing

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