A new strategy to study neuroblastoma

MCT Research Talks

Neuroblastoma is a cancer of the nervous system that primarily affects children aged 5 and younger. Although neuroblastoma accounts for only 5% of childhood cancers, it is responsible for approximately 15% of childhood cancer deaths. For children with high-risk neuroblastoma – children in which cancer has spread significantly – the outlook is extremely poor. Approximately 1 in 5 of these children will not respond to treatment, and of those that do, 50% will develop drug resistance leading, in many cases, to death.

Dr Olga Piskareva, an NCRC supported scientist and Honorary Lecturer at RCSI, has recently published a study describing a new way to grow cancer cells in the lab. Traditionally, researchers grow cancer cells in the flasks on the flat surface. This is not the way cells grow in the human body. Dr Piskareva in collaboration with Dr Curtin and Prof O’Brien has designed a new way to grow cancer cells that recreate their growth in 3 dimensions as in the human or mice body. They used special cotton wool like sponges as a new home for cancer cells and populated them with cancer cells. At the next step, they gave cells the drug at the different amount and checked what happened. In this system, cells responded only to the drug at doses used in the clinic or mice models.

This new strategy to grow cells on sponges should help to understand cancer cell behaviour better and accelerate the discovery and development of new effective drugs for neuroblastoma and other cancers. This, in turn, will make the outlook for little patients better and improve their quality of life.

Dr Olga Piskareva and her research group

More details about our research can be found in Dr Piskareva’s blog!

Reported by Olga Piskareva

FcgRIIa –an attractive target to control immune response

MCT Research Talks

Our group is a drug discovery lab currently working on the development of a novel Fc gamma receptor IIa inhibitors. FcgRIIa is a low affinity receptor for Fc portion of immunoglobulin G (IgG) and is implicated in a variety of conditions that are still mainly untreatable, such as rheumatoid arthritis, lupus, immune thrombocytopenia, sepsis. FcgRIIa is widely expressed by human innate immune cells, and is the only Fc gamma receptor found on human platelets.

Mainly over-stimulation of the FcgRIIa receptor in these conditions that leads to the progression of the disease. For example, in sepsis the platelets get activated via FcgRIIa in response to bacteria present in the blood, which results in thrombocytopenia and disseminated immune coagulopathy. This causes, not only internal haemorrhage but also formation of blood clots that block peripheral blood vessels leading to sepsis-associated limb loss, heart attacks and/or strokes. Using a targeted approach, such as pharmacophore modelling, our group has developed a small molecule compound that effectively blocks FcgRIIa-mediated platelet aggregation in vitro. In agreement with the chosen targeted approach, this compound was shown to bind to the FcgRIIa directly and possesses specificity for the FcgRII subgroup of the Fcg receptors.

Ultimately, this compound has a great potential to be used for treatment of other FcgRIIa-mediated auto-immune conditions, such as rheumatoid arthritis, lupus and an array of immune thrombocytopenia conditions.

Prof Dermot Cox, Dr Tatiana Devine and Padraig Norton