New Research Uncovers How Deadly Childhood Cancer Grows, Highlights Two Potential Therapeutic Targets
Key Insights
Rhabdomyosarcoma (search) accounts for approximately 50% of all pediatric soft tissue sarcomas and 8% of all childhood cancers, with only a 20%–30% survival rate once metastasized.
University of Houston researchers identified TAK1 protein and the IRE1α-XBP1 (search) stress-response pathway as key drivers of rhabdomyosarcoma (search) tumor growth in two Nature journal publications.
Blocking either TAK1 or the IRE1α-XBP1 (search) axis slowed tumor growth and promoted differentiation of cancer cells into normal muscle cells.
A cancer researcher at the University of Houston has identified key molecular mechanisms that drive the growth of rhabdomyosarcoma (search), a rare and often fatal soft tissue cancer affecting young children, revealing two promising targets for future drug therapies.
Rhabdomyosarcoma (search) accounts for approximately 50% of all pediatric soft tissue sarcomas and 8% of all childhood cancers. The disease carries a grim prognosis when it spreads beyond its primary site, with only a 20%–30% survival rate for patients with metastatic disease. In rhabdomyosarcoma, immature muscle cells fail to develop normally and instead grow into malignant tumors.
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, details the molecular underpinnings of this aggressive cancer.
TAK1: A Culprit Driving Tumor Growth
Kumar and his team identified a protein inside rhabdomyosarcoma (search) cells called TAK1 (Transforming growth factor β-activated kinase 1) that plays a central role in helping tumors grow. The research demonstrates that TAK1 is a previously unrecognized contributor to rhabdomyosarcoma proliferation and differentiation blockade.
"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," said Kumar.
IRE1α-XBP1 (search): A Stress-Response Pathway Hijacked by Cancer
In a complementary discovery, the researchers found that rhabdomyosarcoma (search) tumor cells rely on a cellular stress-response pathway called IRE1α-XBP1 (search) to survive. This axis appears to be critical for maintaining the malignant state of the cancer cells.
"IRE1α-XBP1 (search) axis is a critical regulator of RMS growth, differentiation, and chemosensitivity, and supports its therapeutic targeting in RMS," Kumar stated.
Therapeutic Implications
Blocking either TAK1 or the IRE1α-XBP1 (search) pathway slowed tumor growth and helped the cancer cells develop into normal muscle cells, suggesting that pharmacological inhibition of these targets could restore normal differentiation and halt disease progression. Collectively, these findings identify two new targets for drug therapies.
Disease Background
There are two distinct types of rhabdomyosarcoma (search). 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 such as those in the arms or legs.
The research is supported by a $3.2 million grant from the National Institutes of Health, underscoring the significance of this work in addressing an urgent unmet medical need in pediatric oncology.