image: Ashok Kumar, Else and Philip Hargrove Endowed Professor of Drug Discovery at the University of Houston College of Pharmacy and director of the Institute of Muscle Biology and Cachexia, has received $3.2 million from the NIH to tackle Rhabdomyosarcoma, a malignant soft tissue sarcoma that has a higher incidence in young children, accounting for 8% of all pediatric cancers.
Credit: University of Houston
The tragedy of cancer is profound, but it feels even more devastating when it affects children, cutting into lives just beginning and dreams yet to unfold. A $3.2 million grant from the National Institutes of Health is empowering University of Houston researchers to tackle this devastating reality by finding new ways to treat Rhabdomyosarcoma, a malignant soft tissue sarcoma that has a higher incidence in young children, accounting for 8% of all pediatric cancers.
The survival rate for patients with RMS that has metastasized to other parts of the body is only about 20%–30%.
“Our project will identify key mechanisms and molecular targets to prevent tumor progression in RMS patients in future therapies,” said Ashok Kumar, Else and Philip Hargrove Endowed Professor of Drug Discovery at the UH College of Pharmacy and director of the Institute of Muscle Biology and Cachexia. “We are looking for a key factor that causes tumors to grow and prevents the cancer cells from maturing into normal muscle cells.”
RMS cells, found most often in muscle tissue, keep growing and dividing uncontrollably, never developing into a final form.
Tackling the target
Inside RMS cells is a protein called TAK1 (Transforming growth factor β-activated kinase 1), which plays a key role in regulating cell growth.
"Though the role of TAK1 in RMS or any other sarcoma has not been investigated, our preliminary results demonstrate that TAK1 is highly activated in both embryonal RMS and alveolar RMS cells and human RMS samples, suggesting it plays a significant role in this cancer,” said Kumar.
Embryonal RMS is more common in younger children and tends to grow in areas like the head, neck or genitals. Alveolar RMS is more aggressive and often affects older children and teenagers, usually appearing in large muscles like those in the arms or legs.
“Blocking TAK1, either by changing the genes (genetic approaches) or using drugs (pharmacological approaches), can stop certain harmful behaviors in cancer cells,” said Kumar. “This was tested both in lab-grown cells and in living models, showing that TAK1 is a key target to control RMS cancer’s spread and aggressiveness, and inhibits tumor formation.”
Unraveling the mystery
For scientists, the mysteries still to be unraveled are how TAK1 actually helps RMS cancer grow and why it stops RMS cells from maturing into normal muscle cells. Also, therapeutic potential of inhibition of TAK1 in RMS has not yet been examined.
“Based on our preliminary studies, we hypothesize that aberrant activation of TAK1 causes tumorigenesis and growth of RMS and inhibition of TAK1 can be a potential therapeutic approach for RMS.
By targeting TAK1, we aim to stop the cancer at its source and help the cells develop normally. This approach could lead to new and better treatments for RMS," said Kumar.