Notch Cell Signaling Pathway Linked To Brain Tumors In Children

In one of the latest developments in cell signaling research, the cell communication pathway known as Notch has been linked to a type of brain tumor that occurs in children. In a study recently published in the Journal of Neuropathology & Experimental Neurology, it was announced that Notch genes were ‘overexpressed’ in cases of pilocytic astrocytoma (PA).


Although one of most commonly occurring types of tumors in children, PA is a relatively rare disease. Considered a low-grade, slow-growing brain tumor, PA has been diagnosed in 15% of all primary brain tumors cases in adolescents and children. According to statistics gathered by the Central Brain Tumor Registry of the United States, one out of 100,000 children in the United States develops PA every year.


PA is commonly treated via surgery, which can be an effective solution. However, many cases of PA involve tumor growth in hard-to-reach areas of the brain. Left untreated, PA eventually results in seizures, loss of vision, and difficulty with physical coordination.


The discovery of Notch’s significance with regard to tumor growth was made by a research team headed by Fausto Rodriguez, M.D. of the John Hopkins Kimmel Cancer Center. Rodriguez, who is also an associate professor of pathology at the Johns Hopkins University School of Medicine, said that the discovery of the pathway’s actions was made during a comparison of the amount of RNA produced by the genes–in a process known as ‘expression’–which occurs in brain tissue. The study involved both healthy tissue and samples from patients with PA.


The results of the study showed that one or more of the genes found in the Notch pathway were overexpressed in almost all 22 samples obtained from PA brain tissue. In comparison, the healthy brain cells showed normal levels of expression. Of the 22 samples, four to 21 showed signs of overexpression. Proteins closely related to Notch–HES1 in particular–were also detected in 58 out of 61 additional brain tissue samples. Of those samples, 40 displayed expression in varying degrees.


Rodriguez further explained the Notch pathway as a basic signaling path that enables cellular communication during the development stage. Doctors already know that cancer triggers the abnormal activation of signaling pathways, effectively spurring on the growth of tumor cells and ensuring its survival. According to Rodriguez, the results of the new study support that discovery, and that the actions of the Notch pathway have been identified in cancers such as leukemia and breast cancer.


Co-authored by Charles Eberhart, M.D., also of John Hopkins, the study also revealed the significance of the Notch pathway in cases of medulloblastoma and glioblastoma, two other types of brain cancer that have a significantly higher risk of death than PA. According to Rodriguez, their study conclusively proved that Notch was abnormally active in low-grade tumors such as PA. He also suggests that Notch may one day serve as the primary target in the treatment of PA and other tumors for which surgery is dangerous and/or impossible due to the location of the tumor.

Cell-Signaling Molecules Show Potential For Slowing Down Cancer

Researchers at the Laura and Isaac Perlmutter Cancer Center knew they were on to something big when they embarked on a series of studies involving the effects of specific genetic material on tumors. The research team from the NYU Langone Medical Center was after all familiar with the potential of genetic material–specifically the non-coding variety–for tumor treatment.


But probably what not everyone realized was that their research would form the bulk of one of the largest studies on the effects of cell signaling molecules on melanoma cancer cells. In the study, two bits of genetic material were identified in melanoma tumors, both of which showed tremendous potential for halting the spread of the cancer–a significant finding indeed, and one that would have long-term implications on future approaches to treating the disease.


In a report published in the online Journal of the National Cancer Institute on February 11, researchers revealed that the identification of microRNAs–particularly miR-382 and miR-516b–could be crucial for the future targeting of melanoma cells that have a high likelihood of spreading and causing the demise of the patient.


The results of the cell signaling study have a number of potentially valuable implications for melanoma research and related studies. In the wake of the initial cell signaling study, the same team has already embarked on subsequent studies into microRNAs that may have similar value with regard to identifying melanoma cases in which there is a high likelihood of the disease spreading to the brain. These incidents have been linked with almost 50% of melanoma-related fatalities.


The Laura and Isaac Perlmutter Cancer Center team analyzed 800 microRNAs that seemed to suppress cancer growth. These cell signaling molecules were found in tumor cells of 92 male and female melanoma patients, 48 of whom had rapid cancer progression. All the patients agreed to donate the samples to the NYU Langone research database.


The senior investigator of the study, Eva Hernando, PhD, said that their research revealed the cancer suppressing effects of two types of microRNA in melanoma cases. This effect is less apparent in primary tumors of an aggressive nature. According to Dr. Hernando, the next step for the team is to show how the results gathered in such tests could be used to identify patients that have a higher chance of the melanoma progressing aggressively. Doctors could also use the information to determine whether early aggressive treatment will improve melanoma patients’ chances for survival.


Melanoma is one of the most common types of cancer in the world. In the United States alone, 73, 870 new cases of melanoma are expected to occur in 2015. This figure is culled from data gathered by the American Cancer Society, which also estimates that almost 9,940 melanoma-related deaths will occur in the same time frame.


Perhaps the most promising realizations to come out of all this is the possibility that the effect of microRNAs with regard to suppressing melanoma tumor growth will apply to other types of cancer as well. When that happens, the global medical community may just have a potent new weapon in the fight against cancer.