Lab Update: Spring 2016

I am very proud to be working in the Children’s Brain Tumor Project laboratory, and quite astounded at how fast the initiative has grown. I was appointed as a Fellow in 2012, when I was assigned to work on the role of bone-marrow-derived cells in low-grade glioma transformation. Today, I’m honored to lead the daily operation of our lab’s partnership with the Weill Cornell Institute for Precision Medicine (IPM), which allows us to do exactly the sort of personalized medicine that we dreamed about just a few years ago.

Thanks to the IPM, we can now offer genomic sequencing to every single child treated here for a brain or spinal tumor—at no cost to the family. Before surgery (whether it’s a biopsy or resection), the patient provides a cheek swab or blood sample to capture data on his or her normal DNA. Then, during surgery, small specimens of any tumor tissue removed are sent to the team at the IPM core facility for further DNA analysis.

Technical specialists at the IPM extract DNA from these specimens so they can analyze the genome, then screen for mutations among 500 known cancer genes. After they perform the initial sequencing, they generate a report and send it back to me to analyze. It is my responsibility to evaluate the data within this report and search for clues as to how those mutations might best be addressed. I perform extensive research across the scientific literature in search of publications that have identified potential drugs or other treatment options that may be effective in this particular patient against these specific mutations. I also look at specific genomic mutations in each patient and compare them across all cancer cohorts, using new streamlined “big data” portals such as the cBioPortal for Cancer Genomics at Memorial Sloan Kettering, The Cancer Genome Atlas (TCGA) run by the National Cancer Institute, and the U.K.-based COSMIC catalogue.

After a comprehensive chart review of the patient’s medical history and disease course, I present the findings to our multidisciplinary tumor board, which consists of scientists, physicians, surgeons, pathologists, and systems biologists. The tumor board reviews the findings from my case presentation and may determine the best treatment options. If there are clinical trials available at any institution across the country that may be appropriate for the patient, we will identify them.

Finally, the results of the sequencing and the recommendations of the tumor board are presented to the patient and family by the managing pediatric neuro-oncology team to help guide their decision-making process. As the Pediatric Brain Tumor Precision Medicine Fellow, it is my most important responsibility to make sure the family is informed of all recommendations that may result from the tumor board meeting.

Of course, there is still more progress that needs to be made in this relatively new field of personalized medicine. Many of the tumors that we have sequenced and the mutations we’ve identified still do not have effective treatments. We need to identify more targetable mutations and more efficacious drugs and/or drug combinations. Once we understand an individual tumor on the molecular level, we will be able to better choose the right agent to utilize for that patient. One thing we have learned from our sequencing efforts is that each tumor is biologically unique, which is crucial to understanding the molecular underpinnings of the disease. This realization also changes our approach to treatment and may ultimately lead to a better outcome for patients in the future.

We are working hard right now on planning the next steps in this important project. We have just recently injected tumor specimens from select patients into mouse brains. Our goal is to use these mice to model the disease and ultimately test combinatorial agents that may prolong survival in these animals. The agents we identify with the best response in these animals could then be tested for safety and effectiveness in patients.

All of us here at the CBTP are working furiously toward the day when we can apply what we’re learning in the lab to our patient population. Our thoughts are always with the children and their families. Every day, even as we get closer to the answers we need, families continue to hear a diagnosis without hope. We know that our job is creating that hope, and we know we could not do it without you and your generous support.

Prajwal Rajappa, M.D.
Precision Medicine Fellow, Children’s Brain Tumor Project