Houston researcher identifies new targets for fatal rhabdomyosarcoma

 A cancer researcher at the University of Houston is reporting what makes malignant soft tissue cancer grow in children, identifying key mechanisms and molecular targets to prevent tumor progression in patients in future therapies of the fatal rhabdomyosarcoma. 

A rare soft tissue cancer that has a higher incidence in young children, rhabdomyosarcoma accounts for approximately 50% of all pediatric soft tissue sarcomas, 8% of all childhood cancers and has only a 20%–30% survival rate for patients with the disease when it has metastasized to other parts of the body. In the disease, immature muscle cells grow into tumors when they fail to develop normally. 

In two new articles published in Nature journals, 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, explains how a protein inside RMS cells, called TAK1 (Transforming growth factor β-activated kinase 1) is a culprit found in rhabdomyosarcoma tumors helping them grow. After further research, he reports that the tumor cells rely on a cellular stress-response pathway called IRE1α-XBP1 to survive. Blocking either Tak1 or IRE1α-XBP1 slowed tumor growth and helped the cancer cells develop into normal muscle cells. 

Collectively, these findings identify two new targets for drug therapies. 

IRE1α-XBP1 axis is a critical regulator of RMS growth, differentiation, and chemosensitivity, and supports its therapeutic targeting in RMS. These findings also uncover a previously unrecognized role for TAK1 in RMS growth and differentiation, and suggest that TAK1 can be a potential therapeutic target for the treatment of RMS." 

Ashok Kumar, Else and Philip Hargrove Endowed Professor of Drug Discovery, UH College of Pharmacy

There are two types of rhabdomyosarcomas. 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. 

The research is supported by a $3.2 million grant from the National Institutes of Health.