From Comments from David Pratt, MD, radiation oncologist with OHC. Article by Maria Cohut, Medical News Today
October 23, 2018
October is Liver Cancer Awareness Month. For many health care providers, it can serve as a reminder that liver cancer is a leading cause of cancer deaths worldwide, according to the American Cancer Society, and it accounts for more than 600,000 deaths each year. It tends to grow and expand at a fast rate, so if it isn’t caught early, it means that people who have been diagnosed with it may not survive longer than 11 months.
Some good news: Researchers from many international institutions have teamed up to design a more effective drug for liver cancer therapy. Their compound may help improve survival rates and reduce adverse effects.
Adult primary liver cancer is a disease in which malignant (cancer) cells form in the tissues of the liver. There are two types of adult primary liver cancer: hepatocellular carcinoma and cholangiocarcinoma.
“With liver cancer, doctors typically use surgery, radiation and a drug called sorafenib,” said David Pratt, MD, radiation oncologist with OHC. “The problem is, this drug typically adds only three months to survival, and it can have severe side effects.”
In an effort to improve liver cancer treatment, researchers from the Cancer Institute of Singapore have come together with colleagues from other global institutions to develop a new experimental drug, which they call “FFW.”
FFW, the scientists believe, could hinder the growth of primary liver cancer and help reduce the unwanted effects of typical treatment.
“In our latest work, [we have] demonstrated an effective strategy to accurately target oncogenes previously considered undruggable,” says study co-author Professor Daniel Tenen, MD, of the National University of Singapore.
Oncogenes are genes that in certain circumstances can transform a cell into a tumor cell. When they are deemed “undruggable” it means they do not respond to drugs that target them.
The researchers based their new study on some earlier findings about a protein that is known to be implicated in tumor growth: SALL4. SALL4 is seen in developing fetuses but is normally inactive in fully developed tissue. However, in liver cancer, this protein becomes active again, contributing to tumor growth.
So far, SALL4 has been considered an “undruggable target.” That’s because, unlike other proteins, SALL4 does not have a “pocket” in its structure to allow drug molecules to lodge in and take effect. Nevertheless, the research team’s earlier experiments suggested a way to work around this issue.
“In our earlier research, we found out that the SALL4 protein works with another protein, NuRD, to form a partnership that is crucial for the development of cancers such as [hepatocellular carcinoma],” explains Prof. Tenen.
“Instead of looking for ‘pockets’ on SALL4, our research team designed a biomolecule to block the interaction between SALL4 and NuRD,” he adds.
By blocking the interaction between SALL4 and NuRD, the biomolecule FFW “has led to tumor cell death and reduced movement of tumor cells,” Prof. Tenen observes. Moreover, when used in conjunction with sorafenib, FFW may also be able to hinder the growth of liver cancer that is resistant to this drug.
The researchers’ experimental compound is a peptide drug. Compared with small molecule drugs, peptide drugs act with more precision, which also means that it is potentially less toxic; it will not affect healthy tissue.
“When it comes to treating cancer, we have three primary goals: remove or stop the growth of the tumor or cancer cells, cause little or no harm to health tissues, and for the patient to experience as few side effects as possible,” explained Dr. Pratt. “If this drug is successful, it will achieve these three goals, and hopefully give patients an extended survival period.”
If the researchers perfect the peptide drug — and perhaps develop other, similar compounds — they hope to use them to tackle a series of other cancers that are SALL4-dependent.
“This is fascinating research. Plus, at OHC, we currently have an open trial that is evaluating the efficacy and safety of another drug for patients with advanced or metastatic cholangiocarcinoma whose condition is inoperable and previous treatments didn’t work,” Dr. Pratt noted. “Research and clinical trials are so crucial in our work to eradicate cancer. Or at least provide better treatments that will prolong a quality life.”
For more information about treatment for liver cancer, click here or call OHC at 800-710-4674.
The researchers outline the process of developing FFW in a paper published in the Journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), the official scientific journal of the National Academy of Sciences.
