Cancer drug shows promise reducing hearing loss
Also: New study on Mediterranean diet and prostate cancer
February 1, 2021 | View PDF
Cancer drug repurposed may help protect against hearing loss
According to the World Health Organization, around 466 million people worldwide have disabling hearing loss, a number the organization projects will double by 2050 to affect 1 in 10 people. However, a new study out of Creighton University School of Medicine has identified a drug that has the potential to protect against or treat hearing loss.
The findings are significant because no such FDA-approved drug currently exists, and the drug that has shown effectiveness to protect hearing in animal models, dabrafenib, is an FDA-approved drug that is currently used to treat cancer. Repurposing FDA-approved drugs is an attractive and effective alternative because it can significantly reduce the development timeline and cost of making them available to the public compared to new chemical compounds.
Permanent hearing loss is a major side effect cancer patients experience after undergoing cisplatin chemotherapy, affecting 40% to 60% of people who receive the treatment. Dabrafenib is a medication that can be taken orally to combat cancers with an activated gene called BRAF, such as melanoma, small-cell lung carcinoma, and thyroid and biliary tract cancers. Creighton scientists and students involved in the research found that dabrafenib can be repurposed to prevent cisplatin- and noise-induced hearing loss in mice. Six other drugs in the BRAF signaling pathway also showed significant protection from cisplatin-induced cell loss.
Since dabrafenib has already gone through cancer clinical trials and its side effects are known and relatively minimal, it is a good candidate to advance through hearing clinical trials, said group leader Tal Teitz, PhD, who is an assistant professor in Creighton University’s Department of Pharmacology and Neuroscience, School of Medicine, Omaha, Nebraska.
“There are many types of hearing loss that are caused by cisplatin treatment, noise exposure, antibiotics and aging. Our idea was that there could be some common cellular pathways between these different forms of hearing loss,” said Teitz. “It’s very exciting that we were able to identify a drug that was effective in protecting against noise-induced and cisplatin-induced hearing loss.”
The study also tested whether dabrafenib protects from noise-induced hearing loss. Before exposing mice to 100 decibels (the noise level typical of a running lawnmower) for two hours (enough to cause permanent hearing loss) they were treated with dabrafenib. Significant hearing protection was achieved. Since noise exposure is often unpredictable, the study also examined if dabrafenib could provide hearing protection after damaging noise exposure. Mice were given dabrafenib treatment starting 24 hours after noise exposure, administered alone and in combination with the compound AZD5438, another oral drug the group identified for hearing protection.
The drugs demonstrated hearing protection in mice after noise exposure, and full protection was achieved with the drug combination. The researchers noted that existing surgical treatments for hearing loss, such as cochlear implants, are highly invasive and expensive and this may be a much easier and more cost-effective approach.
Mediterranean diet may help combat prostate cancer
A new study by researchers from The University of Texas MD Anderson Cancer Center is suggesting that following a Mediterranean diet may a good weapon against prostate cancer. A Mediterranean diet emphasizes legumes, fruits, vegetables, whole grains, fish and olive oil and moderation for dairy products and wine.
“Men with prostate cancer are motivated to find a way to impact the advancement of their disease and improve their quality of life,” said study investigator Dr. Justin Gregg, who is an assistant professor of Urology at MD Anderson Cancer Center, Houston, Texas. “A Mediterranean diet is non-invasive, good for overall health and, as shown by this study, has the potential to affect the progression of their cancer.”
The new study looked at men with localized prostate cancer on active surveillance. After adjusting for factors known to increase risk of cancer getting worse over time, such as age, prostate-specific antigen (PSA) and tumor volume, men with a diet that contained more fruits, vegetables, legumes, cereals and fish had a reduced risk of their prostate cancer growing or advancing to a point where many would consider active treatment. The researchers also examined the effect of diabetes and statin use and found a similar risk reduction in these patient groups.
The study, whose largest number of participants were white, also found that the effect of a Mediterranean diet was more pronounced in African American participants and others who self-identified as non-white. These findings are significant as the rate of prostate cancer diagnosis is more than 50% higher in African American men, who also have a higher risk of prostate cancer death and disease progression.
“The Mediterranean diet consistently has been linked to lower risk of cancer, cardiovascular disease and mortality. This study in men with early-stage prostate cancer gets us another step closer to providing evidence-based dietary recommendations to optimize outcomes in cancer patients,” said senior study author Carrie Daniel-MacDougall, PhD, who is an associate professor of Epidemiology at MD Anderson Cancer Center.
After skin cancer, prostate cancer is the most common cancer in men in the United States. Since most cases are low-risk disease, localized to the prostate and have favorable outcomes, many men do not need immediate treatment and opt for active surveillance. Treatments for prostate cancer can cause changes in quality of life and declines in urinary and sexual function, so there is great interest in finding modifiable factors for men managed by active surveillance.
The study followed 410 men on an active surveillance protocol. Trial participants were 82.9% Caucasian, 8.1% Black and 9% other or unknown. The median age was 64, and 15% of the men were diabetic and 44% used statins. The men completed a 170-item baseline food frequency questionnaire, and Mediterranean diet score was calculated for each participant across nine energy-adjusted food groups. The participants were then divided into three groups of high, medium and low adherence to the diet.
After adjustments for age and clinical characteristics, researchers saw a significant association between high baseline diet score and lower risk of cancer grade progression. For every one-point increase in the Mediterranean diet score, researchers observed a >10% lower risk of progression. After a median follow-up of 36 months, 76 men saw their cancer progress. Future research is needed to see if the same effects are seen for larger and more diverse patient groups and men with higher-risk prostate cancer.
“Our findings suggest that consistently following a diet rich in plant foods, fish and a healthy balance of monounsaturated fats may be beneficial for men diagnosed with early-stage prostate cancer,” said Dr. Gregg. “We are hopeful that these results, paired with additional research and future validation, will encourage patients to adapt a healthy lifestyle.”
John Schieszer is an award-winning national journalist and radio and podcast broadcaster of The Medical Minute. He can be reached at firstname.lastname@example.org.