Research

Estíbaliz López Rodrigo, MD

We are grateful for the endeavors of our research fellow, Dr. Estíbaliz López Rodrigo. Dr. Rodrigo has over ten years of experience in the medical field, and is currently a clinical fellow at Memorial Sloan Kettering Cancer Center in New York City.

You can discover our previous research endeavors below.

Research News

Exciting Announcements from Dr. Paul Meyers

 

This has been another productive year for research in the sarcomas of children and young adults:

  1. Sri Ambati is a former incumbent of the Margaux Grossman Fellowship. Sri is working in the laboratory of Dr. Malcolm Moore. Dr. Moore is one of the world’s foremost researchers in the area of cancer stem cells. Sri has shown that inhibitors of heat shock protein are effective in suppressing these Ewing sarcoma stem cells. Sri attended a highly competitive workshop sponsored by the American Association for Cancer Research and designed a clinical trial of this inhibitor to be tested in young patients with recurrent Ewing sarcoma. He completed a protocol for the clinical trial, which is being approved by the Institutional Review Board, and we hope to move very soon toward a clinical trial of a completely new drug attacking a completely novel target in patients with Ewing sarcoma. Every step of this groundbreaking research was supported completely by the generous donations of the Margaux’s Miracle Foundation.
  2. Heather Magnan is a former incumbent of the Margaux Grossman Fellowship. Heather has been successful in developing several new therapies. Her protocol for the treatment of desmoplastic small round cell tumor is actively accruing patients. She developed a novel form of therapy for desmoid tumors that was approved for use by the Children’s Oncology Group, the national organization that coordinates clinical trials for children with cancer throughout the United States and Canada. Heather developed our next generation therapy for Ewing sarcoma. She built upon the success we showed in treating children and young adults whose Ewing sarcoma had recurred following initial therapy. She has designed a trial for newly diagnosed patients with Ewing sarcoma that incorporates into our initial therapy the two drugs that achieved a high rate of response in patients with recurrent Ewing sarcoma. This trial has proved so exciting to patients and to referring physicians that it is accruing well ahead of schedule. We will learn soon if this enhanced therapy will lead to improved outcome for children and young adults with Ewing sarcoma.
  3. Working with Dr. Nai-Kong Cheung and his colleagues, Dr. Alex Chou has completed testing of a highly specific targeted monoclonal antibody against the GD2 antigen called the 3F8 antibody. Dr. Chou’s work has shown that this antibody can help to control metastases of osteosarcoma, the most common form of primary bone cancer in children and young adults. Dr. Chou has written a clinical trial incorporating the 3F8 antibody into front-line therapy of children and young adults with osteosarcoma.
  4. Neal Shukla is an attending in the Department of Pediatrics. His research has focused on the genomics of pediatric tumors. Using the powerful tools of molecular biology he has identified a previously unknown mutation in a gene that causes rhabdomyosarcoma, a tumor of the soft tissues in children and young adults. Ewing sarcoma is caused by a translocation between two chromosomes that creates a novel DNA sequence unique to the tumor. Dr. Shukla has developed an extremely sensitive assay to test for the presence of this unique sequence in circulating blood. We are testing this technique to see if it will allow us to monitor patients with Ewing sarcoma. This could represent an early warning system of disease recurrence, much more sensitive than Xrays or scans and one that requires only a simple blood test.
  5. Estibaliz Lopez is the current incumbent of the Margaux Grossman Fellowship. Dr Lopez is working the laboratory of Dr. Alexandra Joyner, a world-renowned expert in the field of cancer stem cells. Dr. Lopez is focusing on the hedgehog-signaling pathway to determine how this gene, critical to normal development and to the evolution of cancer, can cause normal stem cells to become malignant. Her work has already discovered important mechanisms to explain the evolution of rhabdomyosarcoma, a soft tissue cancer that arises in children and young adults.

A Word From Sri Ambati

First of all, I am honored to be a research fellow of the Marguax Miracle Foundation for 2011.

My passion for research in oncology began during my medical training in India. When I was a resident at Miami Children’s Hospital I worked closely with a pediatric oncology team, which strengthened my desire to advance the horizons of therapeutic strategies in children with cancer. It did not take too long before I decided to come to Memorial Sloan-Kettering Cancer Center to pursue my fellowship. During my clinical year at MSKCC I noticed that sarcomas pose a major therapeutic challenge and we have yet to make significant progress in this field. I chose to work on Ewing sarcoma in the laboratory of Dr. Malcolm Moore at MSKCC, a pioneer in cancer research and a great mentor. His lab has been at the forefront in identifying cancer stem cells in many tumors and developing therapeutic strategies to target them. I am utilizing the resources available in clinic and lab to improve survival in children with Ewing sarcoma.

Ewing sarcoma is a rare cancer that occurs mainly in children and young adults. It can occur in bone or soft tissue and has high propensity for metastasis – especially to lung, bone and bone marrow. Despite developments in chemotherapeutic regimens, the outcome for metastatic Ewing sarcoma remains poor. It is characterized by specific chromosome translocations and up to 85% of the cases have the t(11;22)(q24;q12) translocation, resulting in a fusion gene between EWS (the EWS gene is on chromosome 22) and FLI1 (Fli-1, a protein that in humans is encoded by the human FLI1 gene aberrant expression is also associated with chromosomal abnormalities in humans). Efforts to identify specific gene targets and understand the transcriptional dysregulation have been difficult due to the unknown nature of the cell of origin. We are trying to solve this puzzle in the laboratory by transforming benign mesenchymal progenitor cells into sarcomas to see if we can ascertain exactly what changes are necessary for a normal stem cell to become malignant.

We are planning to introduce “second hits” to inactivate cell death pathways activated in response to DNA damage (siRNAl to p53, RB, BCL2), and to inactivate other potential tumor suppressor genes. We are studying the expression of various surface markers and genes that are over-expressed in Ewing sarcoma during transformation. We are also exploring tumor-stroma interactions in Ewing sarcoma to discover novel targets. We hope that our research will lead to identification of new drugs that will specifically aim at cancer stem cells and improve outcomes in Ewing sarcoma.

We thank you for supporting our research efforts at Memorial Sloan-Kettering Cancer Center.

Exciting Advancements for 2013

We have many new exciting advancements in pediatric oncology and the research of Ewing’s sarcoma:

  1.  Sri Ambati is the current incumbent of the Margaux Grossman Fellowship.  Sri is working in the laboratory of Dr Malcolm Moore.  Dr Moore is one of the world’s foremost researchers in the area of cancer stem cells.  He has shown that not all the cells in a given tumor are equally dangerous.  A small sub set of the cells in a tumor have a much greater potential to make more cells and to spread to other parts of the body.  These cancer stem cells differ from the far more common cells that make up the vast bulk of cells in a tumor.  They have the ability to elude the common treatments that we use to shrink tumors.  Under Dr Moore’s supervision, Sri has identified the cell that gives rise to Ewing sarcoma tumors in patients.  He has identified the features that make these stem cells unique.  He has shown that inhibitors of heat shock protein are effective in suppressing these Ewing sarcoma stem cells.  His work offers the potential for an entirely novel form of therapy for treatment of Ewing sarcoma which may allow us to improve the outcome for all the young patients who develop this tumor,
  2. Heather Magnan was the previous incumbent of the Margaux Grossman Fellowship.  Heather has been successful in developing several new therapies.  Her protocol for the treatment of desmoplastic small round cell tumor is actively accruing patients.  She developed a novel form of therapy for desmoids tumors that was approved for use by the Children’s Oncology Group, the national organization that coordinates clinical trials for children with cancer throughout the United States and Canada.  She has developed our next generation therapy for Ewing sarcoma.  She built upon the success we showed in treating children and young adults whose Ewing sarcoma had recurred following initial therapy.  She has designed a trial for newly diagnosed patients with Ewing sarcoma that incorporates into our initial therapy the two drugs that achieved a high rate of response in patients with recurrent Ewing sarcoma.  We hope that this new, combined therapy will improve the outcome for all young patients with Ewing sarcoma.
  3. Working with Dr Nai-Kong Cheung and his colleagues, Dr Alex Chou has begun testing a highly specific targeted monoclonal antibody against the GD2 antigen called the 3F8 antibody.  Dr Chou’s work has shown that this antibody can help to control metastases of osteosarcoma, the most common form of primary bone cancer in children and young adults.  If these results can be confirmed, we plan to incorporate the 3F8 monoclonal antibody with chemotherapy as part of the treatment of patients newly diagnosed with osteosarcoma.

Impressive Announcement

It is with tremendous pleasure  to announce that Paul A. Meyers, Vice Chair of Academic Affairs in the Department of Pediatrics, has been named the incumbent of the newly established Robbins Family Chair in Pediatrics.  Dr. Meyers has made vast contributions to sarcoma care in children and young adults and is deeply committed to evaluating new therapies in clinical trials; he is equally dedicated to training the next generation of pediatric oncologists.

An endowed chair represents one of the highest honors Memorial Sloan-Kettering bestows on our most talented faculty.  We are proud to recognize Dr. Meyers, and to continue to support his research and clinical excellence.  His work benefits patients around the world and will have a lasting impact.

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