Molecular cell biologist Dipanjan Basu has spent his career studying signal transduction mechanisms that regulate cell division and cancer.
Today, as research assistant professor of pathology, School of Medicine, Basu is focused on understanding one of the most challenging conditions in the field of pediatric oncology—a rare form of brain neoplasia that has no specific therapy.
Approximately one in every 200,000 children are born with this form of brain neoplasm, which appear as pigmented lesions in the brain. They are classified as clinically benign because the lesions don’t metastasize to other organs. They grow more slowly than other malignant tumors and diffuse as opposed to becoming a solid tumor.
This condition usually starts in the membrane covering the brain and infiltrates into brain parenchyma, affecting areas regulating vital functions. It can also spread to the spinal cord, leading to hydrocephalus, an increase in intracranial pressure. Depending on what areas it impacts, symptoms such as seizures, sensory or motor deficits or cranial palsy may develop.
Because the lesions are also coupled with dark patches on the skin, they are called congenital nevi. They are similar to moles, but when they cover 40-60% of the newborn’s skin, they are known as large or giant congenital melanocytic nevi (L/GCMN).
While giant nevi are typically treated with surgery to alleviate cancer risk, the brain lesions pose greater danger, and a child often starts to experience neurological symptoms within the first two years of life. It is a traumatic experience for both the child and the parent.
According to Basu, a smaller subset of patients—less than 1% of all L/GCMN patients who carry the brain lesions—often develop aggressive, untreatable brain cancer with severe neurological symptoms.
“Most parents are unaware their child has this condition because the presence of a brain lesion can only be seen by scans, which may not be ordered until the child exhibits neurological symptoms such as seizures, abnormal muscle weakness or even paralysis,” says Basu.
“By that time, the prognosis is not good,” he adds. “The condition is nearly 100% fatal. Most of these young patients do not survive more than two or three years after the onset of symptoms.”
Basu and his colleagues are currently working on understanding the underlying molecular mechanisms of development and progression of these congenital neoplasms and developing therapeutic approaches to target such mechanisms. He believes the embryonic environment plays a crucial role in the origin of disease.
More than 10 years ago, working in the division of pediatric pathology, he participated in an effort to establish a repository for tissue samples collected from patients across the country. Using these samples, he accomplished the challenging task of developing three-dimensional culture methods for sustainable in vitro growth of tumor cells isolated from patients' lesions of giant congenital melanocytic nevi and neurocutaneous melanocytosis.
His research using these cells showed that they proliferated clonogenically, like cancer cells, and were sensitive to small molecule inhibitors that target signaling intermediates downstream from oncogenic NRAS but also display behavior similar to that of embryonic cells. Currently, he is working to develop an animal model to understand the contribution of factors in the embryonic environment that may play a role in oncogenesis and disease spread while the fetus is still developing in the womb.
Basu is hopeful that this model will uncover new data relating to the molecular and cellular factors driving tumor growth, progression and malignant transformation and eventually lead to improved outcomes for patients with this rare pediatric disease.