Retinoblastoma: an ambitious project to preserve children’s sight
Retinoblastoma, a tumor of the developing retina, is a highly aggressive cancer, diagnosed on average at the age of 18 months. With around 60 new cases in France every year, it accounts for 3 to 4% of pediatric cancers. All cases of retinoblastoma diagnosed in France are treated at Institut Curie, which is a national reference center, certified by the European Reference Network for Pediatric Oncology ERN PaedCan and one of the top centers worldwide.
Although the recovery rate for this cancer is above 98% in France due to care being given at the earliest possible stage, retinoblastoma very often results in loss of sight or of the eye, and the treatments still frequently have long-term side effects. Around 50% of patients have to undergo enucleation, despite the progress made in conservative treatments (intra-arterial and intra-ocular chemotherapy introduced recently). The current key issues for treatment of retinoblastoma involve development of new diagnostic strategies but also reduction of side effects.
A collaborative international effort led by Institut Curie has just revealed the existence of 2 sub-types of retinoblastoma. In identifying a more aggressive subtype, researchers partly explain the diverse responses to treatment of this cancer (see FOCUS below). Published in the journal Nature Communications, these results have given rise to a new ambitious project.
From molecular analysis to imaging: a multi-scale characterization of retinoblastoma
François Radvanyi, head of the molecular oncology team at Institut Curie and principal investigator on the project, is enthusiastic: “Our research conducted currently on retinoblastoma is becoming more ambitions and multi-scale. Several Institut Curie research teams and hospital departments are now involved in this exciting project. Our collective expertise will be our strength for transforming the treatment of retinoblastoma by characterizing the various tumor cell populations present, and by looking for diagnostic markers to identify them and the appropriate therapies.”
Institut Curie is the leading treatment center for retinoblastoma in France, and is getting all of its hospital departments on board in this new project, including ophthalmology, pediatric oncology, genetics, radiology and pathology. We are all invested in the desire to go further in designing new accurate prognostic factors as well as introducing new treatments for our young patients, towards increasingly conservative techniques and fewer side effects”, adds Prof. François Doz, deputy director of innovation, training and clinical research at Institut Curie’s SIREDO center (Care, Innovation & Research in Childhood, Adolescent and Young-Adult Oncology).
Financed in the amount of €800 K by the Ligue contre le cancer, this new project comprises two main elements:
- Characterizing as accurately as possible the different tumor cell populations present in both retinoblastoma subtypes and their response to treatments via approaches using experimental biology, analyses of “multi-omic” data (genomic, genetic, transcriptomic, epigenetic) and spatial data (immunohistochemistry, spatial transcriptomic, imaging). The expected results should enable us to better use the current therapies, and identify new therapeutic targets suited to each patient.
- Developing and pairing two non-invasive diagnostic methods: the first will be based on analysis of circulating tumor DNA (present in the blood and the aqueous humor) and will allow the tumor to be characterized indirectly. The study of circulating tumor DNA will also improve the diagnosis of genetic predisposition to retinoblastoma (of which 45% of cases are hereditary). The second essential approach of the project involves analyzing magnetic resonance imaging (MRI), both visually and quantitively (texture analysis), to identify in particular the “radiomic” characteristics of the different subtypes of retinoblastoma.
► FOCUS – Discovery of 2 subtypes of retinoblastoma
Two subtypes of retinoblastoma have just been identified and characterized, with one of the subtypes being more aggressive and with higher intra-tumor heterogeneity. Several teams from Institut Curie have just demonstrated this, led by that of François Radvanyi in “molecular oncology” at the “cell biology and cancer” unit (Institut Curie, CNRS, Sorbonne University), with support from the Ligue contre le cancer, Institut de la Vision, and contribution of Argentine and Spanish researchers.
Through molecular analysis and a “multi-omic” approach on a series of 102 retinoblastomas, the researchers identified and characterized two subtypes. Subtype 1, which occurs earlier (at around 11 months), includes most hereditary forms of the disease. Subtype 2, appearing later at around 24 months, is characterized by inter- and intra-tumor heterogeneity. This subtype is also associated with a risk of metastases. This study also shows that the retina’s cone cell is indeed the cell in which the retinoblastoma originates.
The existence of inter- and intra-tumor heterogeneity in the various cell populations is one of the key elements explaining the failure of some therapies. Thus the recognition of these two subtypes of retinoblastoma and their diversity offers promising biological and clinical options for treatment of this pediatric cancer.
Reference: A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression. Jing Liu, Daniela Ottaviani, […] François Radvanyi. Nature Communications volume 12, Article number: 5578 (2021). https://doi.org/10.1038/s41467-021-25792-0
The following are involved in the project at Institut Curie’s research center: the teams of François Radvanyi - Cell biology and cancer unit (Institut Curie, CNRS, Sorbonne university), a team certified by the Ligue contre le cancer; Célio Pouponnot – Signaling, radiobiology and cancer unit (Institut Curie, CNRS, Inserm, Université Paris Saclay), a team certified by the Ligue contre le cancer; Irène Buvat – the Translational imaging in oncology unit (LITO, Institut Curie, Inserm), the “Translational research in pediatric oncology” team (RTOP, Institut Curie, INSERM U830).
Also involved are four Hospital Group departments at Institut Curie: the ophthalmology department (Prof. Nathalie Cassoux) in the surgery department, the center for care and research in childhood, adolescent & young-adult oncology (SIREDO) (Dr. Olivier Delattre), the imaging department (Dr. Hervé Brisse), the diagnostic and theranostic medicine division with the genetics departments (Prof. Dominique Stoppa-Lyonnet) and the pathology laboratory (Dr. Anne-Vincent Salomon). A team from the Institut de la Vision will also take part in this project. The Retinostop association, a long-term funder of research in retinoblastoma, will provide support to the project.
The Ligue contre le cancer :
Aelya Noiret: +336 52 03 13 47 - email@example.com
About Institut Curie
Institut Curie, France’s leading cancer center, combines an internationally-renowned research center with a cutting-edge hospital group, which treats all types of cancer, including the rarest. Founded in 1909 by Marie Curie, Institut Curie’s three sites (Paris, Saint-Cloud and Orsay) are home to over 3,700 researchers, doctors, and healthcare professionals working on its three missions: treatment, research and teaching. A private foundation with public utility status, Institut Curie is authorized to accept donations and bequests, and thanks to the support of its donors, is able to accelerate discoveries and improve patient treatment and quality of life. Find out more at curie.fr
About the Ligue contre le cancer
The leading independent association financing cancer research, the Ligue contre le cancer is an independent non-governmental organization drawing on public generosity and on the commitment of its supporters. With almost 481,000 members and 8,700 volunteers, the Ligue contre le cancer, is a popular movement in the form of a grouping of 103 departmental committees. Together they operate in four complementary areas: research to cure, prevent to protect, support to help, and mobilize to act. Today the Ligue makes the fight against cancer a societal issue that concerns health, economic, social and political stakeholders in all regions. In breaking taboos and overcoming fears, the Ligue is helping to change the image of cancer and of those suffering from it. Find out more: www.ligue-cancer.net