Nhan L. Tran, PhD

Professor, Department of Cancer Biology, Neurological Surgery, and Radiation Oncology

College of Medicine

Mayo Clinic

“Genetics of Invasive Glioblastoma Cells”

Glioblastoma (GBM), the most common adult brain cancer, is among the most genetically heterogeneous,

treatment resistant, and lethal of all human cancers. Despite the genetic heterogeneity, a unifying

characteristic of GBM is aggressive cell invasion into the brain parenchyma, which prevents complete surgical removal, increases the risk profile of adjuvant therapies, and virtually assures tumor recurrence. Recurrent

GBM tumors are generally less sensitive to therapy than the original tumor and in most cases are located in

 critical brain areas, preventing a second surgical resection. Most GBM molecular studies to date focus on

primary, newly diagnosed tumors, and as a consequence our knowledge of recurrent GBM biology is limited. It

 is clear however, that primary and recurrent GBM are in some ways distinct diseases, with the latter tumors reflecting selective pressures exerted by the standard-of-care adjuvant treatment paradigm for primary GBM

tumor treatment (radiation and temozolomide (TMZ). Paradoxically, even though the biology of recurrent GBM

is not fully understood, most of the clinical trials testing new GBM therapeutic agents are in the setting of recurrence. Thus, additional studies focused on recurrent tumors are necessary in order to generate more

molecular information on these tumors and to aid in the development of new therapies that

target these aggressive cells. Accordingly, we have conducted comprehensive genomic and transcriptomic   

analyses of patient-matched primary and recurrent GBM patient tumor core specimens with the goal of

identifying new therapeutic targets for recurrent disease. These initial studies have identified the important

signaling node(s) in recurrent GBM and thus a potential vulnerability for targeted agents.