Researchers have discovered some classes of therapeutics that destroy fibrolamellar tumor cells growing in mice and tested them on human cells extracted from tumors.
Treatment options for the deadly liver cancer, called fibrolamellar carcinoma, are very scarce.
Drugs that work in other liver cancers are not effective in fibrolamellar carcinoma, and while progress has been made in identifying the specific genes involved in driving the growth of fibrolamellar tumors, these discoveries have not yet translated into any treatment.
For now, surgery is the only option for children and young adults with no previous liver conditions.
“Some people need therapy already,” said Sanford M. Simon, head of the Cell Biophysics Laboratory at Rockefeller University in New York City in the United States.
Rockefeller University’s Cellular Biophysics Laboratory is conducting these experiments, but the process could take years, and the children and young adults who are now sick may never enjoy the findings
“We decided to be completely agnostic about what we thought would work – we tried everything. To our surprise, we found some compounds that work very well,” he added.
So his team tested more than five thousand compounds, already approved for other clinical uses or in clinical trials, to see if any could be repurposed to treat fibrolamellar tumors.
In an ideal world, scientists conduct extensive experiments to identify the perfect therapeutic target for a disease and then test a set of drugs in model systems to identify promising treatment options to achieve the chosen target.
Rockefeller University’s Cell Biophysics Laboratory is conducting these experiments, but the process can take years, and the children and young adults who are now sick may never enjoy the discoveries.
So Simon has taken a parallel, expedient approach: after testing an extensive library of drugs on fibrolamellar tumor cells grown in mice over several months, his team has identified some new therapeutic classes that appear to effectively kill fibrolamellar tumor cells.
The results suggest that it may be unnecessary to test drug candidates in cells grown in mice before testing them directly in human cells
In addition, further experiments have provided some molecular explanations as to why these drugs are so effective against a disease that, until now, has confounded doctors treating liver cancer.
“So far, I’ve had to tell patients that we don’t have any drugs that are proven to work,” said Michael V. Ortiz, a pediatric oncologist at Memorial Sloan Kettering Cancer Center and coauthor of the study.
“It’s really exciting that we finally have some promising drugs to test in clinical trials. And since each individual responds differently, it’s particularly exciting that we’ve had multiple results that we can now test in combination with each other,” he continued.
Based on these initial findings, the researchers tested the compounds directly on human cells that were taken from patient tumors and were able to test the cells against their lineage of drug candidates after growing for just a few days, getting results similar to those seen in cells that took months to grow.
“Within three days, we can have informative therapeutic data, which is much faster than previously allowed methods,” said Gadi Lalazar, lead author of the paper.
According to Lalazar, although there are some logistical hurdles, “this could be potentially transformative for the treatment of certain cancers.”
The results suggest that it may be unnecessary to test drug candidates in cells grown in mice before testing them directly in human cells, Futurity writes.
Given these results, doctors may soon be able to biopsy cells from a patient’s tumor and subject those cells to an array of drug candidates until they find the most effective compound for that specific patient. Then they can have the treatment plan ready in a matter of days – transforming the landscape of precision medicine.
“We don’t want to give every person who limps the same treatment – we want it to be ‘precisely targeted’ based on whether they have sprained their ankle, broken a bone, or just have a chip,” Simon said.
The findings were published in the scientific journal Cancer Discovery.
