‘Natural killer’ cells could help target drug resistance in medulloblastoma

The lab of St. Jude Children’s Research Hospital researcher Joshua Johnson maintains research into mechanisms by which natural killer (NK) cells, a type of white blood cell that fights infection, protect neurons from damage and cancer. NK cells are critical to controlling inflammation and fighting infections, but cancer cells such as medulloblastoma (MB) have developed specific therapeutic weaknesses that make them resistant to multiple drugs. “We are working to identify and target these ‘natural killer’ cells, ” says Joshua Johnson, Ph. D., senior author, who is also an instructor in genetics and developmental biology at Baylor College of Medicine. “We have the potential to provide a more targeted approach to treat this disease. “

According to U. S. News & World Report, 46, 600 new cases of pediatric brain cancer are diagnosed daily in the U. S. and roughly 80, 000 cases are thought to be related to benign genetic mutations.

Medulloblastoma is a common brain cancer that frequently affects children and young adults in the southern part of the state. Though it is almost always lethal, the median survival rate of patients in the U. S. is only six months. After a median survival of 16 months, medulloblastoma is categorized as grade IV. Despite its high mortality rate, therapy options are limited. By the time patients are diagnosed, the disease has developed a resistance mechanism that is capable of evading therapies that have been developed over the last 20 years. “Over the past three decades, there has been a paradigm shift when it comes to medulloblastoma treatment. The question was: what are the treatment options? What are the specific systems that medulloblastoma are working to evade? Medulloblastoma cells are frequently de-activated in their non-proliferative stages due to chromosomal aberration. This disrupts the DNA efficiency of these cells, Johnson explains. This causes them to become less aggressive and can lead to long-term survival in most patients. However, in some cases, the de-activation is also accomplished by transplantation of stem cells with the altered DNA capabilities, which may lead to uncontrolled proliferation. “In these cases, the organ does not thrive and the patient experiences permanent immunosuppression, ” explains Johnson.

Now, more than 10 years after the immunohistological finding was made, his research group has uncovered a new way restricting the activity of resistance specific to the disease. “In MD-PD, lung cancer, lung adenocarcinoma, multiple myeloma and known drug-resistant tumor models, we have identified a system that we are able to target with immunotherapies with precision, ” says Kalyani Sonawane, Ph. D., research leader, co-principal investigator on the study and head of the St Jude Department of Pathology Laboratories. “Medulloblastoma is difficult to treat and requires multiple strategies provided that we understand how it works and what it does. “