Gene mutation may lead to treatment for liver cancer

Two genetic mutations in liver cells may drive tumor formation in intrahepatic cholangiocarcinoma (iCCA), the second most common form of liver cancer, according to a research published in the July issue of the journal Nature.

A team led by the Icahn School of Medicine at Mount Sinai and Harvard Medical School has discovered a link between the presence of two mutant proteins IDH1 and IDH2 and cancer. Past studies have found IDH mutations to be among the most common genetic differences seen in patients with iCCA, but how they contribute to cancer development was unknown going into the current effort.

iCCA strikes bile ducts, tube-like structures in the liver that carry bile, which is required for the digestion of food. With so much still unknown about the disease, there is no first-line, standard of care and no successful therapies.

"iCCA is resistant to standard treatments like chemotherapy and radiation," said Josep Maria Llovet, MD, Director of the Liver Cancer Program, Division of Medicine, Icahn School of Medicine at Mount Sinai, and contributing author. "Understanding the molecular mechanism of the disease is the key to finding a treatment that works."

Dr. Llovet and colleagues demonstrated that the expression of mutant IDH in the adult liver of genetically engineered mice impairs liver cell development and liver regeneration – a process in which the responds to injury – and increases the number of cells to form a tumor. Moreover, mutant IDH were found to work with activated KRAS, a gene essential in development, causing the development of premalignant lesions and a progression to metastatic iCCA.

"Our findings provide novel insights into the iCCA and offers a possible treatment option for patients suffering from this fatal disease," said Dr. Llovet.

By pinpointing one pathway of iCCA, this study opens up a new line of investigation to identify biomarkers of the disease. Already, Phase 1 clinical trials are being conducted with specific IDH1/2 mutations. The hope is that results of these and future studies can help doctors make life-saving decisions for their patients.

add to favorites email to friend print save as pdf

Related Stories

Novel gene mutations associated with bile duct cancer

Jan 18, 2012

Investigators at the Massachusetts General Hospital (MGH) Cancer Center have identified a new genetic signature associated with bile duct cancer, a usually deadly tumor for which effective treatment currently is limited. ...

Recommended for you

Decoding the emergence of metastatic cancer stem cells

3 hours ago

In the first study of its kind, Rice University researchers have mapped how information flows through the genetic circuits that cause cancer cells to become metastatic. The research reveals a common pattern ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.