Clinical/Basic Research in the Department of Surgery



Clinical Research

The department of surgery is an integral component of the multimodality treatment of childhood malignancies that have been the mission of St. Jude Children's Research Hospital since its opening in 1963. The department participates in a number St. Jude clinical protocols as well as Children's Oncology Group protocols. While the department has a number of clinical interests, the clinical projects listed below are some of the areas of special interest within the department.

Current solid tumor protocols


Bone tumors
The department has been recognized both internationally and nationally for its limb salvage program in the management of bone tumors. A number of innovative procedures have been developed by the members of the department and they actively participate in many St. Jude protocols.


Melanoma
Melanoma is extremely rare in children, however, the solid tumor division and the department of surgery have been quite active in the management of these children with the development of several St. Jude protocols. The Department of Surgery has established sentinel lymph node biopsy as the standard of care in these children. The management of Spitz nevus has been a special interest since the management of this rare condition is quite controversial.


Neuroblastoma
St. Jude has been a leader in the management of children with neuroblastoma for a number of years and the department of surgery has a specific interest in the management of children with stage 4 neuroblastoma that frequently require quite demanding operative procedures in order to gain gross total resection of these tumors. While this is an area of controversy the Department of Surgery has participated with the solid tumor division in developing protocols for these very challenging children. Over 80% of the children are able to have a gross total resection and it is our feeling that a survival advantage is associated with the performance of a gross total resection especially in children greater than 18 months of age and those children under 18 months of age with N-Myc amplification.


Retinoblastoma
Retinoblastoma represents approximately 3% of childhood cancers and St. Jude is one of the centers of excellence in the United States in management of these children. The ophthalmology division within the Department of Surgery has worked in a collaborative effort amongst many departments within St. Jude to develop a state-of-the-art clinical and research program in the management of these children.


Soft tissue sarcomas
Non-rhabdomyosaracoma soft tissue sarcomas are rare in children but the department has had a long standing interest in the management of these children. In conjunction with the solid tumor division the department participates in the Children's Oncology Group sponsored soft tissue sarcoma protocol which has become the standard, of care in the management of children with non-rhabdomyosarcoma soft tissue sarcomas in the United States.


Wilm's tumor
Bilateral Wilms tumors are extremely rare representing 5% of all Wilms tumor. In the United States there are approximately 25 Wilms tumors treated annually. The department of surgery has had a special interest in this area and has published one of the largest series in the literature. The Division of General Pediatric Surgery and the Division of Urology work together in the management of these very complex patients and have been able to perform nephron sparing procedure in over 80% of the children who have been treated at St. Jude for bilateral Wilms tumors. The department is presently participating with the Children's Oncology Group and is entering patients on the bilateral Wilms tumor protocol.


Basic Research

In addition to meeting the increasing surgical needs for the patients at St. Jude, members of the department of surgery, particularly in the division of general surgery, have a significant research effort, both basic and clinical.

Andrew Davidoff, MD, maintains an active NIH-funded research lab that focuses on angiogenesis and gene therapy, both for cancer therapy and the treatment of monogenetic disorders. Inhibiting the new blood vessel formation (angiogenesis) required for tumor growth has proven to be an effective alternative anti-cancer strategy. However, anti-angiogenic therapies are likely to prevent tumor growth rather than actually kill the tumor cells, and so once the restrictions of angiogenesis inhibition are ended, tumor regrowth may recur. Therefore, Dr. Davidoff is studying the potential of chronic delivery of these agents by gene therapy techniques to maintain anti-tumor activity.

In addition to the work on tumor angiogenesis, Dr. Davidoff’s lab is also focusing on the role of epigenetic changes in pediatric solid tumors, neuroblastoma in particular, in the pathogenesis of these cancers and as potential therapeutic targets. Finally, Dr. Davidoff has a significant ongoing effort in investigating the feasibility of correcting monogenetic disorders of the liver with gene transfer approaches, primarily mediated by adeno-associated viral vectors (AAV). He is currently conducting a clinical trial of AAV-mediated gene therapy for hemophilia B and will soon open a similar clinical trial for the treatment of patients with hemophilia A.

John Sandoval, MD, has also been engaged in basic tumor biology research. Several signal transduction pathways are important for tumorigenesis and he has an active laboratory interest evaluating the role of PI3/Akt and mTOR inhibition in neuroblastoma. Using a targeted approach, Dr. Sandoval is studying the regulation of downstream signaling components and crosstalk with other pathways that could compensate for differential PI3K/Akt signaling in high risk neuroblastoma. In an effort to identify novel therapeutic targets, a combined inhibitory strategy is being developed focusing on multiple signaling components and/or pathways (vertical or horizontal inhibition) looking, in particular, for the most optimal treatment responses and biomarkers for the prediction of PI3/Akt/mTOR drug response in neuroblastoma.

In addition, Dr. Sandoval is characterizing the role of the RAF/MEK/ERK pathway in rhabdomyosarcoma and investigating the critical biologic and molecular features and differences between pediatric and adult melanoma. Employing a combined biochemical and preclinical modeling approach, he hopes to highlight the unmet medical need in these challenging pediatric solid tumors and translate these findings into a more 'personalized' treatment approach toward these childhood malignancies.