Identifican el mecanismo de activación de la vía Hedgehog implicada en el rabdomiosarcoma, un tipo de cáncer infantil

The activation mechanism of the Hedgehog pathway involved in rhabdomyosarcoma, a type of childhood cancer, has been identified

The INCLIVA Translational Pediatric Solid Tumors Research Group and the Childhood and Adolescent Cancer Translational Research Group at the Vall d’Hebron Research Institute (VHIR) have identified one of the mechanisms that promotes oncogenicity in rhabdomyosarcoma, a type of childhood cancer that accounts for 8% of all cancers in boys and girls. 

The researchers, led by Dr. Josep Roma and Dr. Samuel Navarro, have discovered the mechanism that strongly activates the Hedgehog pathway in these tumors, even though they are not themselves mutated in most cases.

Specifically, the study revealed that high levels of Indian Hedgehog (IHH) and Desert Hedgehog (DHH) ligands were present and demonstrates that they play a fundamental role in the oncogenic activation of childhood rhabdomyosarcoma.

The Hedgehog signaling pathway is key to cell proliferation, growth, and differentiation of tumor cells. It also controls tumor cell migratory capacity and the formation of metastases, and therefore, tumor aggressiveness. The oncogenic function of this pathway was already known, but this study has now shown its activation mechanism. Clarifying the molecular mechanism of the activation of this pathway will be key in the development of new, tailored therapies that can be designed with much more specificity if these exact mechanisms are known. Unlike other types of cancer in which genetic mutations have been found in the pathway’s components, Hedgehog signaling is activated in rhabdomyosarcoma because some of the pathway’s ligands are overexpressed. 

“For this study, human rhabdomyosarcoma tumor cell lines were implanted in experimental animal models. We observed that when the cells do not have the appropriate ligands, the tumors could not grow, or their growth was very limited. Therefore, inhibiting the interaction between the ligand and its receptor could be a good therapeutic target”, explained Dr. Josep Roma.

This discovery will allow medium-term alternatives to be offered to rhabdomyosarcoma patients who do not respond to current therapies. In fact, in 2011 one of the same research groups discovered the involvement of another signaling pathway (via Notch) in rhabdomyosarcomas and now “one of their lines of work focusses on the double pharmacological inhibition of both Notch and Hedgehog”, he went on.

This work could be replicated in other types of cancer such as pancreatic, ovarian, or colorectal cancer, where activation of the Hedgehog pathway has also been described.


Research in rhabdomyosarcoma

The aim of pediatric cancer research is to seek highly-effective treatments for the almost 1,000 children who are diagnosed with cancer every year in Spain. Therefore, translational research in this field is fundamental.



This type of childhood cancer affects around 900 children per year in Spain.

Between 80 and 90 tumors per year (8% of the tumors detected), are a rhabdomyosarcomas. These are malignant tumors that can appear in a variety of locations (extremities, head and neck, nose, ears, etc.). In fact, it is the most common type of soft tissue sarcoma in children.

The location and histological and molecular subtype of these tumors affects their aggressiveness, invasiveness, destructiveness, and metastatic capacity. In the most favorable cases there may be a cure rate of 80%–90%. But, if the disease is advanced or presents with metastasis, the prognosis is much less favorable and the cure rate can be much lower, sometimes even below 40%.

Pediatric oncologists and researchers have seen an increase in the survival of childhood cancer over the past 20 years thanks to new, more individualized treatments and better molecular definition of tumors. Even so, 20% of children with cancer are still not cured. 

Scientific publication:

Identifican el mecanismo de activación de la vía Hedgehog implicada en el rabdomiosarcoma, un tipo de cáncer infantil