A drug commonly used to treat HIV patients may be a viable treatment for metastatic cancers, according to findings from a trial recently published in the journal Cancer Discovery. While the study focused on patients with fourth-line metastatic colorectal cancer, the researchers believe these findings could be applied to a variety of other types of cancer. Let’s take a closer look at the findings of this study and what the trial could mean for the future of cancer treatment.
About Lamivudine
This clinical trial focused on the HIV drug lamivudine, which is one of the standard medications used in highly active antiretroviral therapy (HAART), the most common form of modern HIV treatment. HAART was a revolutionary development in the treatment of HIV/AIDS in the mid-1990s, as it can effectively stop the progression of the disease and dramatically improve life expectancy. Lamivudine is also used in the treatment of hepatitis B.
Lamivudine falls into a category of medications called nucleoside reverse transcriptase inhibitors (NRTIs). It is used to decrease levels of HIV (or hepatitis B) in the bloodstream. While it is not a cure for HIV, lamivudine decreases the risk of developing AIDs and other HIV-related illnesses (like serious infections and cancers) in some patients.
Pre-Study Findings
The idea to test lamivudine in cancer patients gradually evolved over the past decade in the lab of study co-senior author David T. Ting of the Massachusetts General Hospital Cancer Center. Ting and his collaborators found that as much as 50 percent of a tumor’s DNA could be made up of “repetitive elements,” often previously referred to as “junk DNA.”
These repetitive elements were only produced in cancer cells. Certain types of cancer, such as colorectal cancers and cancers of the esophagus and lungs, produce especially high numbers of repetitive elements. The elements produce RNA at extremely high levels, which then reproduce through reverse transcription. Ting has referred to this virus-like process as a repeatome.
The repeatome replicates itself through reverse transcription and then travels into the genome, essentially allowing cancer to change the genome. While observing this process, Ting had the idea to test lamivudine as a possible way to interfere with the process.
Preclinical Trials
Ting and his team of researchers evaluated his theory during preclinical studies. They discovered that colorectal cancer cells showed sensitivity to lamivudine, as the drug interfered with the cells’ movement. The researchers also found evidence that the HIV drug caused DNA damage and interferon responses, which showed that an inflammatory response had been triggered in tumor cells.
While not yet evaluated, Ting believes that the findings of the preclinical trials indicate that combining immunotherapy with the use of a reverse transcriptase inhibitor like lamivudine could help immune cells more effectively fight metastatic cancers. He has also speculated that this therapy method could potentially prevent cancer or the recurrence of cancer.
Results of the Trial
The trial evaluated 32 patients with advanced metastatic colon cancer, all of whom had seen their cancers progress after four previous lines of cancer treatments. The patients were given lamivudine.
The first nine patients were given the same standard dosage as HIV patients. According to Ting, administering this dosage resulted in signs of the disease stabilizing. The researchers then adjusted the dosage to four times the standard HIV amount and administered it to the remaining 23 patients, who showed high tolerance.
At the end of the trial, the researchers found that nine of the 32 patients (28 percent) either showed disease stability or a mixed response. The tumors did not shrink, but the research team believes these results show promising evidence that lamivudine can be repurposed for use in anti-cancer therapy for metastatic cancer patients.
Building Off These Findings
This trial began as an investigation into the biology of cancer cells but yielded unexpected and promising results for a potential new form of cancer treatment. According to Ting, it is very rare to produce disease stability in patients with such advanced stages of cancer, especially when that stability was produced through the introduction of a single agent.
The team of researchers hopes to begin a Phase III study in which they would test a three-drug reverse transcriptase inhibitor combination. In the next trials, Ting hopes to evaluate whether HAART, the standard three-drug combination used in modern HIV treatment, can be used as a treatment for metastatic cancers. In addition to expanding the treatment to the full HAART regimen, the researchers hope to determine why certain patients showed better responses than others. While they believe that the results are encouraging, the majority of the patients did not show any significant benefit from receiving lamivudine.