Rhabdoid tumor, a rare but highly aggressive pediatric cancer, is defined by total biallelic inactivation of SMARCB1, a component of the SWI/SNF chromatin remodeling complex. Although rhabdoid tumors are rare, more than 20% of all cancers have a mutation in the SWI/SNF complex. Thus, finding a viable therapeutic target in rhabdoid tumors may enhance understanding of other cancers. Through previous analysis of 12 rhabdoid cancer cell lines, it was revealed that a majority of lines overexpress receptor tyrosine kinases (RTKs), and consequently, are susceptible to treatment with compounds targeting specific RTKs.
In this study, we used cell viability assays to test the effect of a range of RTK inhibitor compounds, such as imatinib, across these 12 rhabdoid cancer cell lines. Additionally, western blots were used to verify that cell lines expressed decreased levels of RTK downstream targets after treatment with compound. In addition, a thirteenth cell line, KP-MRT-RY, was characterized through screening against an informer set of 440 compounds and a phospho-RTK array revealing specific overexpressed RTKs. These in vitro experimental results reveal rhabdoid cell lines are vulnerable to inhibition of overexpressed RTKs and suggest further pursuing RTK inhibitors as a therapeutic treatment for rhabdoid tumors in clinical trials.
PROJECT: Targeting rhabdoid tumors with small-molecule RTK inhibitors
Being at the Broad this summer revealed how broad, yet interdependent science is becoming. By engaging with a diverse network of scientists, clinicians, mentors and faculty members, I have expanded my definition of science as a career. Conducting cutting-edge human health research at the Broad has made me excited to see where my combined passions for medicine and research will lead in helping to solve today’s paramount health problems.