The group of  Translational Research in Cancer in Childhood and Adolescence of the Vall d'Hebron Research Institute (VHIR) has identified one of the mechanisms that promote the oncogenicity in rhabdomyosarcoma, a type of childhood cancer which accounts for 8% of all cancers in children and teenagers.

The researchers, led by Dr. Josep Roma, principal investigator of the research group, and Dr. Soledad Gallego, head of the Paediatric Haematology and Oncology Department of Vall d'Hebron, have discovered what is the mechanism that makes the Hedgehog route to be strongly activated in these tumours even without introducing direct mutations in most cases. Specifically, the study reveals a high presence of Indian Hedgehog (IHH) and Desert Hedgehog (DHH) ligands and demonstrates that they play a key role in the oncogenic activation of childhood rhabdomyosarcomas. It has been published in the British Journal of Cancer.

The Hedgehog signalling route plays a key role in cell proliferation, differentiation and growth of tumour cells. Also controls their migratory ability and metastasis formation and, therefore, the aggressiveness that characterizes them. The oncogenic function of this route was already known, but this study has showed which is its activation mechanism. Clarify the molecular mechanism will be key for the development of new specific therapies, which could be designed with a higher degree of specificity once the exact mechanism is revealed. Unlike other types of cancer, in rhabdomyosarcoma, activation is due to an overexpression of some of the ligands of the route rather than to genetic mutations of its components.

"To carry out the study, they introduce human tumour cell lines of rhabdomyosarcoma (RMS) in animal models of experimentation and observed that when the cells did not have the ligands, the tumours could not grow or their growth was very limited. Therefore, to inhibit the interaction between ligands and their receptor could be a good therapeutic target," explains Dr. Josep Roma.

This discovery will provide medium-term alternatives for patients who do not respond to current therapies. In fact, in the year 2011, this same research group discovered the involvement of another signalling route - via Notch- in rhabdomyosarcoma and now "one of the lines of work they have underway is focused on getting the double pharmacological inhibition of these two routes, Notch and Hedgehog," he advances.

On the other hand, this work, in which the translational research group of paediatric solid tumours of the INCLIVA Health Research Institute has also participated, could be replicated in other types of cancer such as pancreas, ovarian and colorectal where the activation of the Hedgehog route has also been described.

Research on rhabdomyosarcoma

The paediatric cancer research at VHIR aims to find highly effective treatments for almost a thousand children who, every year, in Spain, are diagnosed with cancer and thus, the translational research in this field is important.

So much so that for 15 years there is a line of children's sarcoma research within the laboratory of translational research in paediatric cancer at VHIR.

During 2011 they discovered the implication of a signalling route -Notch route- in the aggressiveness, invasive ability and metastasis of rhabdomyosarcoma. In 2012 their research leads them to identify two new proteins (Integrin &alpha,2-and N-cadherin) involved in the process of metastasis of the tumour.

The rhabdomyosarcoma

Childhood cancer affects about 900 infants every year in Spain. 8% of the tumours detected, between 80 and 90 per year, are rhabdomyosarcoma. These are malignant tumours that can appear in a variety of locations (limbs, head and neck, nose, ears, etc.). In fact, it is the most common type of soft tissue sarcoma in children.

Depending on its location and histological and molecular subtypes, they will be more or less aggressive, with more invasive, destructive or metastatic capacity. In the most favourable cases there may be a healing rate of 80-90%. However, if the disease is in an advanced phase or it appears with metastasis, the prognosis is much more unfavourable and the rate may be much lower, even below 40%.Paediatric 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 a better molecular definition of the tumour. Even so, 20% of children with cancer still don't heal.