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At St. Jude Children’s Research Hospital, science is the not-so-secret weapon in our battle to find cures and save children. This year, we took aim at some enormous challenges that required bold thinking on the best ways to understand, treat and defeat cancer and other deadly diseases.
While we advanced on numerous fronts in the past year, we made particular progress in three strategic areas: genomic (or personalized) medicine, immunology and survivorship.
In the rapidly evolving arena of personalized medicine, St. Jude continues to lead the way with rigorous genomic and pharmacogenomic science focused on childhood cancer, with more than more than a dozen genomics-related papers published in top peer-reviewed journals in the past year.
The best treatment of some childhood cancers may vary depending on the individual’s inherited genome, the genomic fingerprint of their specific cancer, and the molecular markers that can predict a child’s likelihood of successfully responding to medications. The science involved in each of these three arenas is specialized and complex, and we’ve made significant impacts in each of these areas this year.
Inherited genomics: A study published in March 2013 linked inherited variations in a few genes to increased risk of acute lymphoblastic leukemia, which helps explain why Hispanic children have a higher incidence of this cancer.
Cancer genomics: The St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project has dramatically advanced our understanding of the genetic basis of childhood cancer and has led us to new potential treatment options for a variety of aggressive childhood cancers. Nearly 100 researchers are involved in this effort. Among our discoveries was identificationof a gene mutation that provides the first clue about the genetic basis of a form of neuroblastoma that usually strikes adolescents, teens and young adults, suggesting it is a subtype of the tumor that requires different treatment strategies. We found that a startling 78 percent of an aggressive brainstem tumor carried changes in two genes not previously linked to cancer. We also identified mutations in several different childhood tumors that are targeted by drugs already in development. These are just a few of the exciting discoveries that would not have been possible without sequencing the entire genomes of more than 700 patients with some of the most aggressive childhood cancers.
Pharmacogenomics: Pharmacogenomics focuses on understanding how genes affect a person’s response to drugs. Through the ongoing PG4KDS study, we are using the science to help guide patient therapy and are beginning to realize the promise of personalized medicine. Nearly 1,500 patients have enrolled in the study, which involves checking a blood sample for variations in 225 genes that play a role in how an individual responds to drugs. Currently, results for four of those genes are included in patient medical records, where computer tools developed for the study make it easier for clinicians to incorporate results from the genetic test into prescribing decisions. Over time, we anticipate more genes to be added to patient files, increasing the tools that enable us to personalize treatment.
Data sharing: Just a year after St. Jude made history with the largest-ever release of comprehensive human cancer genome data to the international scientific community; we joined a global alliance working to expand sharing of genomic and clinical data. The consortium encompasses more than 70 health care, research and disease advocacy organizations with representatives in more than 40 countries. We have long advocated for greater sharing of data, and are hopeful this effort will lead to standards that make such sharing easier and more commonplace. Regardless, we will continue to do all we can to rapidly share our discoveries with others to maximize our impact and inspire additional discoveries for the benefit of children everywhere.
While our focus is on cancer, it is important to note that genomic research has far-reaching benefits. For example, there is increasing evidence that cancer and degenerative diseases may have common origins. This year, our researchers studying these links found some new important connections, but also discovered mutations in two genes that have important implications for ALS, or Lou Gehrig's disease.
In the field of immunology, St. Jude scientists are leading the field in research involving specialized T cells that are essential for a balanced immune system. One of these studies discovered elements of how these T cells work that should aid efforts to develop new drugs for use in organ transplantation or for treatment of autoimmune disorders. Another study revealed the way in which T cells serve to match immune response to the level of threat, which in turn helps us better figure out ways to respond when the system fails. And a third identified a potential new way to fight bacterial infections by targeting a specific immune system protein, rather than the infection itself.
As cure rates for childhood cancer have improved, there are an increasing number of adults who are childhood cancer survivors. By understanding the long-term effects of the treatments used to cure childhood cancer, we can continuously improve treatments and offer survivors valuable insights into protecting their health. This spring, we published results from a one-of-a-kind study that brings former St. Jude patients back to campus for complete medical assessments. Results based on more than 1,700 of these assessments found thatchildhood cancer survivors overwhelmingly experience a significant amount of undiagnosed, serious disease as adults. The types of risks vary by the treatment the individual received. The study had dramatic benefits for many of the participants, as the assessments identified many previously undiagnosed conditions, such as serious issues like breast cancer and heart problems. This allowed the survivors to take action to protect their health. Meanwhile, St. Jude remains a leader in efforts to ensure that young cancer patients thrive as well as survive. We showed the world that pediatric ALL can be cured with cranial irradiation. St. Jude researchers are now working on new strategies to help young cancer survivors ease or possibly avoid the side effects of treatment now and in the future.
Beyond our research, St Jude continues to advocate for children facing cancer, regardless of where they are treated. We consulted on patients from all 50 states as well as abroad. Our faculty also played a key role in spotlighting the ongoing shortage of cancer drugs, including a national study that connects higher rates of relapse in pediatric cancer patients to a drug shortage, St. Jude experts have offered congressional testimony on the need for solutions to this ongoing shortage.
St. Jude investigators featured in 2012-2013 highlights above: