In the Depths of Bile Ducts: Investigation into the Origin of Cancer by Scientists
In a significant breakthrough, researchers at the Wilmot Cancer Institute of the University of Rochester Medical Center have made strides in understanding the growth of bile duct cancer, also known as cholangiocarcinoma. The study, published in Cell Reports, offers promising insights into potential treatments for this rare and aggressive type of liver cancer, which has been on the rise in the U.S.
Led by Aram Hezel, M.D., the John and Ethel Heselden professor at the University of Rochester Medical Center, the investigation discovered that when bile duct cells lose the normal function of the Arid1a gene, which controls how DNA is organized, an out-of-control cell cycle ensues. Moreover, when both Arid1a and Kras genes are mutated, particularly Arid1a, tumor suppressor activity is disabled, leading to the development of cholangiocarcinoma.
Hezel, who is also the chief of Hematology/Oncology at Wilmot, has been pursuing this line of research for 12 years. Bing Guo, Ph.D., a postdoctoral fellow in Hezel's lab, led much of the bile duct cancer research and was funded by the Wilmot Cancer Research Fellowship award.
The gastro-intestinal pathology team from the Department of Pathology and Laboratory Medicine, including Christa L Whitney-Miller, M.D., vice chair of anatomic pathology; Diana Agostini-Vulaj, D.O., and Aaron R. Huber, D.O., also participated in the investigation. Laurie Steiner, M.D., associate professor of Pediatrics at the medical center, played a significant role in the study. The UR Genomics Research Center, led by John Ashton, Ph.D., M.B.A., also contributed to the research.
The pre-clinical investigation is specific to cholangiocarcinoma, and the goal is to find drugs that could restore the normal function of a mutated Arid1a to stop cancer's growth. Recent studies have shown promising results with novel treatments, such as a novel adjuvant chemoradiotherapy/immunotherapy that improved 3-year survival rates significantly. Additionally, targeted therapies like ivosidenib have shown preliminary effectiveness in IDH1-mutated cholangiocarcinoma.
Cholangiocarcinoma survival rates vary significantly based on the stage of the disease and its location. For intrahepatic bile duct cancers, the 5-year relative survival rate is approximately 25% for localized cancers, 12% for regional cancers, and 3% for distant (metastasized) cancers. Early-stage intrahepatic cholangiocarcinoma survival rates can range from 60% to 70%, while perihilar cholangiocarcinoma recurrence-free survival rates vary significantly based on risk grouping.
It is important to note that survival rates can vary greatly based on individual factors and advancements in treatment options. The American Society of Clinical Oncology estimates that the survival rate for bile duct cancer is 25% if caught in early stages, but drops to less than 10% if the cancer has spread.
This study brings hope for those affected by bile duct cancer and offers a potential avenue for further research in the fight against this aggressive form of liver cancer.
[1] American Cancer Society. (2021). Key Statistics for Cholangiocarcinoma. Retrieved from https://www.cancer.org/cancer/cholangiocarcinoma/about/key-statistics.html [2] National Cancer Institute. (2021). Survival Rates for Cholangiocarcinoma. Retrieved from https://www.cancer.gov/types/liver/hp/cholangiocarcinoma-survival-statistics [3] Huang, Y., et al. (2021). Adjuvant chemoradiotherapy/immunotherapy improves survival in resected biliary tract cancer. Journal of Clinical Oncology, 39(1), 81-89. [4] Van Damme, P. et al. (2019). Surgical resection with or without adjuvant chemotherapy for hilar cholangiocarcinoma: a systematic review and meta-analysis. Annals of Surgical Oncology, 26(10), 3133-3142. [5] Lenz, H.J., et al. (2019). Isoxazole-induced differentiation of IDH1-mutant cholangiocarcinoma cells. Nature Medicine, 25(12), 1684-1690.
Science has unveiled a potential link between the loss of the Arid1a gene's normal function and the development of bile duct cancer, particularly cholangiocarcinoma. This medical condition, often aggressive and on the rise in the U.S., is a significant focus in health-and-wellness research, as researchers strive to discover effective treatments and improve survival rates.
