The latest research conducted by investigators at UT Southwestern has helped in unveiling important revelations regarding a special protein that is associated with deadly forms of thyroid cancer and many other cancers in human body. Researchers at UT Southwestern identified a protein that was once considered a “CNS-specific” protein, but through a series of experiments conducted on laboratory mice, is now observed that an over-expression of this protein is associated with medullary thyroid carcinoma (by hyper-secreting certain neuroendocrine hormones)
The results of this research published online in scientific journal Cancer Cell.
The research team identified that controlling or modulating the activities of this protein can help in devising effective and functional therapeutic strategies against certain cancers. These implications are mainly directed at the management of neuroendocrine tumors that arise at a distance from brain and include malignancies of the lungs and pancreas.
One of the co-authors of the paper and professor of Surgery at UT Southwestern, Dr. Fiemu Nwariaku, commented:
“Once or twice a month, patients come to UT Southwestern, often complaining of soreness or a swollen throat. When the diagnosis is a rare and incurable form of thyroid cancer called medullary thyroid carcinoma, it is always distressing for the patient – and for me – because we currently have no real therapies that truly extend life in these unfortunate cases.”
The study identified that approximately 25% of all the medullary thyroid cancers were caused by genetic mutations or aberrations (for which genetic counseling and periodic screening was practiced in families with a history or genetic risk of medullary thyroid cancers), however, little was known about the causative agents responsible for the remaining 75% of the tumors.
The research team at UT Southwestern has long been studying the mechanism and possible pathogenesis of medullary carcinoma of the thyroid; however breakthrough advancement occured when Department of Psychiatry at UT Southwestern made an important discovery while studying the molecular mechanisms of Alzheimer’s disease. Associate Professor of Psychiatry and Neurology and Neurotherapeutics, Dr. James Bibb, along with his associates developed a transgenic model to study dementia and other brain disorders in mice. This was accomplished by inducing brain injury via overexpression of a brain specific protein – referred to as Cdk5. During the course of experimentation, the research team identified that mice developed medullary carcinoma of the thyroid (which was being studied by Dr. Nwariaku) in previously normal mice.
Dr. Nwariaku and Dr Bibb collaborated in initiating a study to identify the role of Cdk5 in the pathogenesis of medullary carcinoma of the thyroid (both in mice and human subjects). The team discovered that the protein is not specific to brain cells (as it was previously believed) and also occurs naturally in C cells of thyroid. In some cases, the protein metabolism extends beyond the normal controls of C cells leading to medullary carcinoma of thyroid.
Dr. Bibb said:
“There are currently two FDA-approved drugs for treating neuroendocrine cancers, but neither of them blocks this specific pathway – one this study has shown to be a crucial vulnerability in the cancer, if appropriately targeted. We were surprised, but encouraged, by the finding because they link the human nervous system to disease processes that include the toughest of all foes, cancer.”
Although the overall incidence of medullary thyroid cancers is rare, the prognosis is generally poor, and surgery is extensive, often requiring excision of large areas of involved tissue or the entire thyroid gland (along with a part of normal tissue around the tumor). It is, however, unfortunate that most cases of thyroid medullary cancer are reported at fairly advanced stages (when the cancer cells have already metastasized to other tissues).
Latest advancements and future goals:
Currently, scientists of UT Southwestern are collaborating with Drs. Bibb and Nwariaku to understand the pathogenesis and learn more about devising innovative treatment strategies for the management of a variety of endocrine malignancies.
Dr Bibb said:
‘This research is ongoing, and we are now identifying precisely how Cdk5 causes the growth and spread of these forms of cancer with the goal of discovering new drugs, which we can test in our animal model. We want to work together to translate our laboratory bench-derived insight into treatments that help cancer patients. We also think we will learn more about brain injury by studying this cancer.”
The research, which is funded by the American Cancer Society, is also supported by other researchers, such as Professor of Pathology, Molecular Biology, and Plastic Surgery, Dr. James Richardson and Associate Professor of Radiology, Dr. Xiankai Sun.
Photo from mayoclinic.org