Our dollars go to Nino Rainusso, MD at Texas Children’s Cancer Center.

There are approximately 1700 new cases of pediatric sarcomas each year in the U.S. Although 70% of patients with localized disease can be cured with multi-modality therapy, which includes several rounds of intense chemotherapy, aggressive surgical resection and radiation therapy, almost all children with recurrent or metastatic disease would die. In other words, 500 children with sarcoma will succumb due to cancer progression and many more would have to deal with the long-term consequences of their cancer treatment. Therefore, novel therapeutic approaches are desperately needed to improve the dismal outcome of sarcoma patients who present with metastatic or recurrent disease.

Our laboratory has developed a research project that combines personalized medicine, cancer genomics and pre-clinical drug testing concepts. We have collected fresh sarcoma specimens from every child diagnosed or treated at Texas Children’s Hospital and developed an “avatar” or patient derived tumor xenograft mouse model. Basically, a small piece of the same tumor that arises in a sarcoma patient is surgically implanted in one or two mice. These mice do not have an immune system and implanted tumors can grow after several weeks.  We anticipate that both tumors – patient sarcoma and mouse-grown sarcoma – would carry the same biological features:  same tumor histology, same genomic signature and same biologic properties. Moreover, we can select available drugs, based on tumor genetics and biology, which are most likely to be safe and effective in any particular mouse-grown tumor.

If a drug or drug combination work well in treating the “avatar” mouse, it is likely to have a beneficial effect on the patient.  The success of this approach depends in obtaining tumor samples in a timely manner and rapid genomic validation (original tumor and xenograft tumors should share the same histology, genomic and biological properties). We have observed that sarcoma specimens collected from our patients and patient derived tumor xenografts maintain the same tumor histological features. Currently, we are in the process to “genomically” validate more than 30 patient derived tumor xenografts.  We would like to use the additional research funds to expedite the process and to develop more “avatars”. We have already started testing the effect of new drugs and immunotherapy in patient derived tumor xenografts collected in our institution with encouraging results.

Our long-term plan is to conduct co-clinical trials where the information generated from patient derived tumor xenograft experiments (“avatar” mice) would guide the treatment in our children with sarcoma. We expect that this therapeutic approach would increase the success rate in very aggressive type of tumors and decrease treatment toxicity in less aggressive cancers.