2-drug combo reduces lung cancer tumor size in mice
- Lung cancer is the second most common form of cancer worldwide.
- Each year, around 2 million people receive a lung cancer diagnosis, and 1.8 million people die of the disease.
- There are two types of lung cancer — small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) — with NSCLC causing the majority of cases.
- NSCLC can be treated with surgery, radiation, and chemotherapy, but is rarely cured.
- Now, research has found that, in mice with NSCLC, a combination of two drugs reduces tumor size and number, a finding that may lead to clinical trials in people.
According to the American Cancer Society, lung cancer is the second most common cancer diagnosed in the United States.
It is also the leading cause of cancer deaths, accounting for one in five deaths from cancer‚ more than colon, breast, and prostate cancers combined.
Most lung cancer cases are diagnosed in older people, with the average age of diagnosis being 70 years. The good news is that cases are falling as fewer people are smoking tobacco, which causes more than 80% of lung cancers.
However, some 2 million people around the world still receive a lung cancer diagnosis each year.
About 85% of cases are non-small cell lung cancers (NSCLCs). As chemotherapy and immunotherapy are not particularly effective against this type of lung cancer, new treatments are urgently required.
Now, a team from the Salk Institute and Northwestern University has found that a combination of two drugs, one already licensed by the Food and Drug Administration (FDA), and the other currently in clinical trials, reduced tumor size and number in mice with NSCLC.
The research is published in Science Advances.
Need for new treatments
“This treatment would be effective for patients with KRAS/LKB1 mutant lung adenocarcinoma,” said Dr. Lillian Eichner, a lead author on the study, and assistant professor of biochemistry and molecular genetics at Northwestern University.
“Each year in the U.S., there are [about] 20,000 new cases of this molecular subtype of the disease,” she noted. “Current survival time is on average 10 months from initial diagnosis for patients with this devastating disease, and improved therapeutic approaches are sorely needed.”
The researchers identified histone deacetylase (HDAC) inhibitors as a potential treatment for this type of lung cancer. HDAC inhibitors are epigenetic regulators that have been shown to slow tumor growth in animals.
The study authors established that HDAC3 was critical for the growth of hard-to-treat LKB1-mutant tumors, so they then looked at whether pharmacologically blocking HDAC3 might affect tumor growth.
In this study, they used two different drugs — the HDAC1/HDAC3 inhibitor entinostat, currently in trials, and a MEK inhibitor, trametinib, already FDA-approved — to treat KRAS/LKB1 mutant NSCLC in mice.
Drug combo significantly reduced tumors
The researchers gave the mice entinostat, trametinib, or a combination of the two drugs by oral gavage — a tube directly into the stomach or small intestine — for 42 days.
At the end of the 42 days, they assessed tumor growth.
They found that neither drug alone reduced the growth of tumors. However, the combined treatment significantly reduced tumor burden compared to all other treatment groups.
As Dr. Eichner told Medical News Today: “We found that two clinically well-tolerated targeted therapies, a MEK inhibitor and an HDAC inhibitor — neither of which are chemotherapy — together elicit therapeutic benefit, i.e., significantly slow tumor growth. Both drugs are clinically well-tolerated, but neither [is] effective at slowing lung cancer growth when administered individually.”
Mice given the combined treatment had 79% less tumor area and 63% fewer tumors in their lungs than untreated mice.
Human trials needed
These drugs are already being used to treat cancers. Trametinib first received FDA approval in 2013 for the treatment of metastatic malignant melanoma. It was approved for the treatment of NSCLC in 2017.
Entinostat has not yet been approved by the FDA for clinical use, but has undergone both phase 1 and 2 clinical trials. There are also ongoing phase 3 trials in breast cancer patients. In the trials, people have generally tolerated the drug well.
The drugs have not yet been used together in people. Dr. Eichner outlined the next steps in assessing the combined therapy.
“A phase 1 clinical trial would come first, to assess the safety of this combination therapy approach,” she explained.
“Our preclinical studies were very encouraging with regard to [the] safety of this drug combination, and based on the established safety profiles of both drugs, we are hopeful that this would also be the case in people,” said Dr. Eichner.
“A phase 2 study would subsequently assess whether this combination slows tumor growth and extends [the] lifespan of this group of patients,” she added.
New hope for cancer patients
Drug development is a lengthy and costly process, with a recent study reporting an average investment of $1.3 billion to bring a new drug to market.
And new cancer drugs take, on average, 6 to 12 years from discovery to approval. So finding new ways to use existing drugs is both cost-effective and faster.
“Our study finds that existing cancer treatments that didn’t originally work may be effective if repurposed. Our work provides an example of how understanding basic tumor biology can lead to new approaches for cancer treatment, sometimes even without the necessity to develop new drugs, which can be a slow process.”
– Dr. Lillian Eichner
Although it is early days, their findings could lead to new treatments for this hard-to-treat lung cancer. More research is needed to confirm the findings, but Dr. Eichner is optimistic.
“Our findings suggest that treating patients simultaneously with both of these existing and available drugs could help slow the growth of lung tumors for this group of patients,” she told MNT.
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