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ADVANCE Discourse: Lab

A Pivotal First Step

Published July 10, 2014 3:01 PM by Michael Jones

Researchers from the Icahn School of Medicine at Mount Sinai and Harvard Medical School recently discovered a connection between a form of liver cancer and two mutations in the IDH gene. Intrahepatic cholangiocarinoma (iCCA) is the second most common form of liver cancer. Although there had previously been evidence of IDH mutations in patients with iCCA, this study marks the first time the exact genes, IDH1 and IDH2, have been targeted and identified specifically as a direct link. An story from Newswise detailed the study and subsequent findings.

“Our findings provide novel insights into the development of iCCA and offers a possible treatment option for patients suffering from this fatal disease,” said Josep Maria Llovet, MD, director of the liver cancer program at Mount Sinai’s Icahn School of Medicine, in the article.

The study demonstrated the effect of mutated IDH genes using mice, showing a decrease in the liver’s ability to health itself and an increase in “the number of cells to form a tumor. The gene mutations also resulted in a relationship with the KRAS gene, which is known to be linked to the development of cancer. The combination of these factors leads to formations of malignant legions in a liver with weakened defenses and, eventually, iCCA. According to the story, targeting IDH1 and IDH2 as pathways for iCCA has already resulted in new clinical trials to determine their impact on iCCA patients.

“iCCA is resistant to standard treatments like chemotherapy and radiation,” explained Llovet. “Understanding the molecular mechanism of the disease is the key to finding a treatment that works.”

Although the article pointed out, “there is no first-line, standard of care and no successful therapies” for patients with iCCA, the study has provided a necessary first step in the development of a treatment for the disease. The discovery has opened the door for further investigation into a relatively mysterious cancer and could potentially lead not only towards a broader understanding, but also a successful therapy. 


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