Pursuing new treatments for Neuroblastoma children

Dear Cure First and Project Neuroblastoma supporters,

Last month, I had the amazing opportunity to present my work at the Annual Meeting of the American Association of Cancer Research (AACR) in Chicago where 20,000 scientists came together to present their most up-to-date research. My poster: “Pediatric Cancer: organoid patient derived cells guide personalized neuroblastoma treatments” was well received and resulted in fruitful discussions that will help bring this exciting project to the finish line. This was also a great opportunity to catch up with our collaborator Dr. John Maris from Children’s Hospital of Philadelphia, who was enthusiastic about our results as well.

Our initial results with the Informer Set drug library (320 compounds) highlighted that each sample was unique as well as and the cancer pathways involved in neuroblastoma (NB).  Scientific rigor requires to repeat the screens, this time with an updated, clinically relevant library (PARIS library: 120 FDA approved drugs). Indeed, I found additional NB patient derived samples to the one mentioned in our January report, which are extremely sensitive to the same targeted agent, that is FDA approved for ovarian and breast cancer. Whereas these targeted agents’ sensitivity in one of our model is well explained by mutations in the DNA repair pathway, the other samples responding to them don’t have any alterations in this pathway. This is a great example of how functional drug screening is an effective approach for the discovery of drug responses overcoming what cannot yet be explained by genomic data alone. The data analysis was carried on with the help of an App made by our analyst Hallie Swan, where all the drug screenings results are incorporated and available to browse.  

We confirmed the original pathological diagnosis using immune-histochemical staining and FISH (Fluorescence in Situ Hybridization) for the MYCN status. This data was generated thanks to an amazing collaboration with Chantal Pauli MD at the Institute of Pathology and Molecular Pathology of Zurich (Switzerland).

The next step to successfully bring our findings into the clinic is the validation with an in vivo study, in other words, in living mice. We designed a research study where mice with NB tumors will be treated with inhibitors to the DNA repair pathway to test their efficacy. This in vivo study is needed to eventually initiate a clinical trial and ultimately make this treatment available for children with NB. In order to proceed with this ambitious plan, we need your help: we are launching a fundraising campaign to collect the necessary funds to make the in vivo study possible. Please help us by donating and spreading the word about our work on new, targeted treatments for neuroblastoma. By contributing to this project, you are advancing novel, less toxic and more effective treatments in the fight against neuroblastoma.

We look forward to reporting our results to you and advancing a cure for this devastating childhood cancer.

Thanks for all your extensive support,

Dear Cure First and Project Neuroblastoma supporters,

In December the scientific board of Cure First met to receive an update on the progresses that we made in 2017. We not only presented our most recent findings, but also highlighted the essential support that you were able to give us making the Neuroblastoma project possible. Thanks to your support, we obtained crucial results which will directly impact the lives of patients and help the scientific community to better understand this disease.

I like to start the new year by reflecting on the impact that the results of our NBL project will have on the future of medicine. There is a high rate of failure in cancer therapies. Many of the drugs will never make it to market because their efficacy can only be proven in a small subset of patients enrolled in the clinical trial. But nevertheless, these drugs would have the potential to help some patients, we just have to find the right drug for the right patient. To increase success, we could pre-screen the cancer therapies in patient derived live cells, instead of testing drugs in cells lines, that they do not recapitulate the behavior of cancer cells. Testing the drugs directly into cancer patient derived organoids (3D mini-cancers in a dish), before we decide on a therapy for the patient, is the right approach to deliver personalized treatments.

I’m very excited to announce, that thanks to your help, we got one step closer to do exactly this. We tested more than 400 different drugs on cancer organoids from 9 NBL patients in our collaborative project with CHOP (Dr. John Maris from the Children Hospital of Philadelphia). The results demonstrate that each of those tumors have unique and non-overlapping drug sensitivities. Currently, sequencing would be used to find these unique sensitivities, but in most cases genomic alterations weren’t concordant with drugs our screen highlighted. This means that mechanisms which make a patient sensitive or resistant to a drug are much more complicated and often cannot be defined by a single mutation. Therefore, genomics is only a small part of the entire cancer picture that tells the patient’s story. That’s why we need to test the drugs on the patient’s cells to find the most efficient treatment. In some of the NBL cases, these drugs are approved to treat completely different types of cancers. Would pediatric oncologists prescribe a drug approved for prostate or ovarian cancer to their patients? In the past the answer was no. However, now with the results of our functional test, showed in Figure 1., where it’s clear that a child cancer is highly sensitive to a group of drugs (PARP inhibitors) that are mainly approved for ovarian cancer, they will start to think about it.

Our compelling results indicate how important personalization of treatments are for cancer patients and we are excited to deliver this innovation to NBL, to make sure every child receives the most efficient treatment in future. We will address the challenges of performing such a test in the next update.

Thanks for all your extensive support,