A new study proposes a combination therapy that may improve the treatment of people with liver cancer. When combined with chemotherapy, this new siRNA approach can target proteins involved in cell death, which has shown to reduce the tumor load in a mouse model of hepatocellular carcinoma, the most common type of primary liver cancer. Considering the lack of conventional treatment for advanced stages of liver cancer, this is a welcomed new step toward developing an effective treatment for this aggressive disease.
So, how does this new approach work?
“What we do is simply turning off a mechanism which prevents cell death, specifically in liver cells,” explains Dominique Leboeuf of Skotech and the first author of this study. “Once the mechanism is turned off, the cells become more susceptible to dying. This allows for the chemotherapy to be more efficient, killing more cancer cells, and preventing them from dividing. And although our siRNA reaches all liver cells, the cancer cells are more sensitive, because they are dividing rapidly, so they will be more affected by the treatment whereas normal cells survive.”
Researchers from Skoltech and MIT have collaborated in this study and drew from diverse expertise in small interfering RNA (siRNA), therapeutic drug delivery, and drug development. Led by professors Konstantin Piatkov, Timofei Zatsepin, and Daniel Anderson, the study combined Piatkov’s knowledge in the N-degron pathway, Zatsepin’s expertise in siRNA and Anderson’s expertise in oligonucleotide drug delivery, explained study co-author Zatsepin.
“Dominique [Leboeuf] confirmed that the suggested molecular mechanisms allow the selective killing of tumor cells while sparing normal cells, which is crucial for further drug development,” he added. “Together with the lab of Dan Anderson in MIT, we were able to show perspectives of this combinatorial approach to treat liver cancer in animal models.”
Of note, an approved treatment for people with advanced liver cancer has only seen a three-month increase in overall survival, highlighting the need to develop novel treatments for this disease. Nonethless the measured increase spells progress.
Beyond developing a new treatment approach to liver cancer, Zatsepin said that combining siRNA with other drugs may provide a solution for many diseases that are difficult to treat.
“Because the proteins targeted by our therapy are expressed in all types of cells, the combinatorial treatment developed in this study has the potential to be applied to all types of cancer,” explained Professor Piatkov, the study’s lead author. “Our approach is simple and universal, and we believe that it has the possibility of eventually improving the outcome for many cancer patients in the future.” As diligent sacrificing healthcare workers across the globe are finally being acknowledged for their tireless life-saving work during this COVID-19 pandemic, at ADRLF we also highlight the researchers behind-the-scenes, within this critical group of medical professionals. Thank you, ALL!
To learn more about this study, click here.
To read more about liver cancer prevention and treatment, visit our blog.