Scientists Discover “Achilles Heel” in Liver Cancer Therapy

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Yaneff_280116Liver cancer is one of the most deadly forms of cancer. It is likely so deadly since it affects the largest organ inside the body—the liver.

In chemotherapy, most cancer cells are killed. However, cancer stem cells can survive and form a new tumor that can withstand a chemotherapy attack.

In a new study published in the journal Cell Metabolism, University of Southern California (USC) researchers have identified the liver cancer stem cells. Scientists believe this discovery can possibly lead to reprogramming the stem cells to allow for more responsive cancer treatment. The hope is that more people will survive from liver cancer.

When cancer originates in the liver cells, it is called primary liver cancer. Hepatocellular carcinoma is another type of liver cancer that affects the liver cells called hepatocytes. When liver cancer starts in the cells that line the bile ducts, it is called cholangiocarcinoma.

How can liver cancer stem cells avoid being resistant to chemotherapy? The goal is to identify the Achilles heel, or the bad seed, during chemotherapy that prevents survival, especially in liver cancer.

The researchers found that the key to prevent liver tumors from multiplying stem cells is to target the stem cell marker called NANOG. It is rare during the early stages of cancer. That being said, it thrives during the third stage of liver cancer. The cancer will then spread after the liver cancer cell metabolism is revamped in the cell’s energy factory—called the mitochondria.

“Even thought we treat patients with chemotherapy, those bad seeds survive and force relapse,” explained lead study author Keigo Machida, who is the associate professor of immunology and molecular microbiology at the Keck School of Medicine at USC. “That’s why we would like to target the bad seeds in cancer to eradicate recurrence problems and metastasis, which is when the cancer spreads to other parts of the body.”

For the study, the research team examined both liver tumors from hundreds of mice and patient-derived stem cells. It is thought to be the first study to determine the carcinogenic pathway of NANOG. As a result, NANOG is considered a target. The removal of the stem cell marker will lead to the elimination of the most common chemotherapy used for liver cancer called sorafenib.

The researchers then examined messenger RNA, protein, and cell metabolism in the liver to learn how NANOG can reprogram the stem cells that promote tumor growth.

The findings from the study set up mitochondria-metabolism targeted therapy for cancer as a potentially promising new treatment for liver cancer. NANOG will reprogram cells using fatty acids instead of glucose.

“In the future, we might be able to give liver cancer patients a shot that will infuse NANOG-targeted therapy into the blood stream,” added Machida. “Wherever blood circulates, we will be able to deliver new instructions to the bad seeds of cancer.”

That is great news, especially with the liver cancer death toll so high compared to liver cancer cases.

Liver cancer has more than tripled since 1980. It is estimated that there will be approximately 39,230 new cases of liver or intrahepatic bile duct cancer cases in 2016, according to the American Cancer Society.

Sources for Today’s Article:
Chen, C.L., et al., “NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism,” Cell Metabolism, 2016; 23(1): 206, doi: 10.1016/j.cmet.2015.12.004.