David Malkin

Administrative Assistant: Arlene Zaldivar, arlene. zaldivar@sickkids.ca

Research Synopsis

Dr. Malkin's research is closely integrated with his clinical field of expertise. Specifically, his research program focuses primarily on genetic mechanisms of childhood cancer susceptibility and the genetic basis of childhood sarcomas (cancers of bone, muscle and other soft tissues). His research team was the first to demonstrate that highly variable regions of DNA, termed copy number variations, are found in excess in the blood of individuals who harbor germline TP53 mutations, both children and adults, at very high risk of developing cancer and may represent the earliest genetic changes that ultimately lead to development of cancer.

In addition, in collaboration with several national and international colleagues, he is studying the genome of children with specific types of brain tumors and sarcomas, using high-resolution genomic platforms, to identify novel genetic biomarkers of disease susceptibility and outcome. Recently, his work has focused on application of this genetic/genomic information to develop rational clinical surveillance and treatment guidelines for children and adults deemed at genetic ‘high risk’ for cancer. In his work on the common pediatric soft tissue tumor, rhabdomyosarcoma, Dr. Malkin has studied the molecular and cell biology pathways that are associated with the development and progression of these cancers, and has identified molecules that might represent viable targets for novel drug therapies.

Dr. Malkin’s research program focuses on understanding the genetic and genomic mechanisms of childhood cancer susceptibility. Recently, his work has addressed the application of genomics to develop rational clinical surveillance and treatment guidelines for children and adults at genetic “high risk” for cancer. Specific research areas include:

• Development of innovative clinical and molecular biomarker (circulating tumor DNA) approaches for early cancer detection in carriers of germline TP53 mutations (Li-Fraumeni syndrome (LFS)).
• Exploration and implementation of pharmacologic interventions to inhibit tumor formation in Trp53-mutant animal models and human TP53 mutation carriers.
• Identification of (epi) genomic events that modify tumor age of onset and phenotype in TP53 mutation carriers.
• Implementation of precision oncology platforms, integrating next generation sequencing with novel clinical trial design, for children with difficult-to-treat cancer.