Emily Slotkin, MD Over the past forty years, intensive combinations of chemotherapy, surgery, and radiation have helped to improve outcomes for those afflicted with rhabdomyosarcoma, but for patients with disease that has spread or does not respond well to these therapies, this aggressive cancer remains very difficult to treat. New methods to attack rhabdomyosarcoma are urgently needed. In our laboratory we are working to change this with the following projects:
1. Rhabdomyosarcoma is sometimes caused by an abnormal genetic event where portions of two chromosomes inappropriately fuse together only in tumor cells. This abnormal event causes changes in cells that result in their rapid and uncontrolled division, making them cancerous. Ideally, medications would kill cells only having these genetic changes, while leaving other healthy cells unharmed. Such specificity is not achievable with standard chemotherapies, and thus far there have been no new medications able to target the genetic changes in rhabdomyosarcoma cancer cells only. In our laboratory, we are working to change this by pioneering several innovative methods to directly target the inappropriately fused chromosomes and thereby kill rhabdomyosarcoma cancer cells. We have developed drugs which identify the malignant cells with extreme precision and impair their function at a basic level. Using compounds which alter RNA, one of the basic building blocks of cells, we are developing new drugs called antisense oligonucleotides. This extremely powerful but exact approach has enormous potential to affect the fundamental biology which we know drives some types of rhabdomyosarcoma cells to grow out of control. Rigorous testing of these drugs is ongoing, and it is the goal of all of us working daily on these novel technologies that they will soon provide more effective and less toxic treatment options for everyone suffering from rhabdomyosarcoma or similar cancers.
2. Research at Memorial Sloan Kettering Cancer Center has shown that treatment with a group of drugs called mTOR inhibitors are very effective for certain adult patients with cancer. The promise of these drugs has yet to be realized for children. Recent work from our laboratory shows that mTOR inhibitors may be particularly effective for children with rhabdomyosarcoma. Currently, we are working with several pharmaceutical companies that manufacture these agents to open a clinical trial that will test these drugs in children.
3. Despite intensive laboratory work, there have few new treatments for rhabdomyosarcoma over the past 20 years. Many people suspect that this may be because our methods of studying pediatric cancers are inefficient and imprecise. To combat this problem, we are using a new method to edit the genetic codes of the cells that we use in our laboratory experiments. This incredibly powerful and innovative tool allows us to precisely change the genome of cells we are testing to better match those of the patients we treat. We hope that these techniques will make our experiments more accurate and therefore more quickly lead to the discovery of effective treatments.