Radiation therapy is part of the standard-of-care treatment regimen for many cancers, including breast and lung. Unfortunately, the treatment can negatively impact healthy tissue, and many patients suffer radiation-induced complications. One example is radiation dermatitis, an inflammation of skin tissue that can adversely affect patients’ quality of life by interrupting treatment, increasing risk of cancer relapse, and negatively impacting cosmetic appearance. In a new article published in Radiation Research, a team of scientists from Baylor College of Medicine discovered a new use for the FDA-approved and widely used class of drug, proton pump inhibitors (PPIs), as a potential therapy.
PPIs control the production of stomach acid and are more commonly used to treat conditions like gastroesophageal reflux disorder and ulcers. The team wanted to evaluate the efficacy of the PPI esomeprazole when reformulated into a topical product. In preclinical studies, they found the drug dramatically improved the appearance of the skin and accelerated wound healing.
“We screened a library of 130,000 compounds in a quest to find candidate drugs that can regulate inflammation and were surprised to find that the entire class of PPIs possesses a previously unappreciated yet potent anti-inflammatory effect,” said Dr. Yohannes Ghebre, senior author of the study, associate professor of radiation biology at Baylor and member of the Dan L Duncan Comprehensive Cancer Center.
Other researchers have studied the effectiveness of pharmacological treatments like corticosteroids, but there is currently no gold standard.
“The use of topical corticosteroids for radiation dermatitis is limited due to the risk of cutaneous atrophy, stretch marks and secondary skin infection,” said study author Dr. Mark Bonnen, former chair of the Department of Radiation Oncology at Baylor and current chair of the Department of Radiation Oncology at the Long School of Medicine at UT Health San Antonio. “Accordingly, there is an unmet clinical need to develop safe and effective topical formulations.”
Over-the-counter remedies also have been tested but do not offer a perfect fix.
“Skin care practices such as cleansing the irradiated area with mild soap and water-based moisturizers, as well as the use of alternative and homeopathic remedies such as aloe vera gel, honey, curcumin, wheatgrass extract cream and almond oil have been evaluated in clinical studies,” said Dr. Michelle Ludwig, associate professor of radiation oncology at Baylor, member of the Dan L Duncan Comprehensive Cancer Center and co-author of the study. “However, the use of almost all of these agents is not recommended either due to lack of efficacy or insufficient clinical data.”
Bonnen said the publication provides proof-of-principle data demonstrating the efficacy of topical PPIs in activating endogenous antioxidant defense mechanisms and mitigating radiation-induced dermal inflammation and scarring in human 3D skin and animal models.
“We hope to soon launch clinical studies to evaluate the efficacy of topical PPI in cancer patients who are at risk of developing radiation dermatitis,” added Bonnen.
Other contributors to this work include Ngoc Pham, Min Wang, Afshin Ebrahimpour, Abdul Hafeez Diwan, Soo Jung Kim, Jared M Newton, Andrew G Sikora, Donald T Donovan, and Vlad Sandulache of Baylor College of Medicine and Jason Bryan of Harris Health System.
This work was supported by the National Institutes of Health (P30 CA125123, F31DE026682), the FDA (1R01FD005109-01A1), the Veterans Affairs Administration (I01 BX004183-01A1), the National Heart, Lung, and Blood Institute (K01HL118683; R01HL137703) and the American Heart Association (17GRNT33460159).