The significance of ALK receptor in the development of various cancer types

As a Wallenberg Scholar, Ruth Palmer aims to understand ALK signaling in developmental and disease contexts. Malfunctioning ALK activation leads to multiple cancer forms, one of which is the childhood cancer neuroblastoma. 

A cell's behavior is governed by signals from both local and distant parts of the body. These signals are detected by receptor proteins, such as receptor tyrosine kinases, present on the surface of each cell. Receptors relay the message through a cascade of signals into the cell, leading to changes in its behavior and identity. One of these receptors is ALK (anaplastic lymphoma kinase), which plays a crucial role in developmental processes in fruit flies, zebrafish, and mice. In humans, it is known that uncontrolled activation of the ALK receptor leads to various types of cancer, including childhood neuroblastoma and lung cancer. By increasing our understanding of the molecular mechanisms that involve ALK, Ruth Palmer and colleagues have been able to contribute to better treatment for these types of cancer.

"Neuroblastoma accounts for 15 percent of childhood cancer mortality today. There are relatively few genetic mutations in neuroblastoma, however, the gene encoding the ALK receptor is mutated in approximately ten percent of cases, a figure that rises in children who relapse," says Ruth Palmer.

Results from Ruth Palmer's research group have contributed to the introduction of new drugs that inhibit the activity of ALK, providing new treatment options for pediatric oncologists treating children with neuroblastoma. Another goal of the research is to explore how these medicines can be made more effective, for example by combination with other inhibitors. The group uses genetically modified models of neuroblastoma, in mice as well as in the fruit fly as research models. These models are important to understand which proteins interact with ALK, how ALK activity reprograms cell function, and where ALK is active during development. These animal models are combined with in-depth analyses and modifications of DNA, RNA, and proteins that identify important underlying molecular events.

"One long term goal is to develop proteomics based assays that will identify ALK activity from tumor samples from patients with neuroblastoma. This would provide a clinically useful complement to todays sophisticated genetic analyses. This is important, as in many primary neuroblastoma cases, the treating doctors do not know which signaling activities drive the disease.," says Ruth Palmer.