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First-in-Kind Trametinib Antiviral Gel Can Fight HPV Precancers and Prevent Progression
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The novel formulation of trametinib has the potential to change the treatment paradigm of human papillomavirus (HPV) and prevent infections before they progress to deadly cancers.
Researchers at the University of New Mexico Comprehensive Cancer Center are designing a gel based on trametinib (Mekinist; Novartis), an FDA-approved treatment for melanoma and other cancers that shuts down the MEK/ERK pathway, to prevent precancers induced by human papillomaviruses (HPV) from progressing.1
HPV infection can lead to the development of a variety of cancers. | Image Credit: © Naeblys - stock.adobe.com
The investigation, led by Michelle Ozbun, PhD, and Jason McConville, PhD, takes its roots in part from prior research underwent in Ozbun’s lab that studied how HPV infects skin cells and causes diseases. Furthermore, despite the availability of vaccines that prevent HPV infections, many individuals remain unprotected, leading to HPVs accounting for nearly 5% of cancers across the world. These factors necessitate better ways of preventing disease, but antiviral treatments have yet to be created.1
Ozbun and her research team previously conducted a study in 2021 of chemical reactions in the MEK/ERK pathway, which encourages skin cells to reproduce. They found that MEK/ERK signaling promotes the oncogenic expression of HPV viral cells; according to the research team, HPVs are adapted to use that signaling pathway to regulate their productive replicative cycles and produce the proteins E6 and E7, which help other cells multiply.1
According to the investigative team, when the MEK/ERK pathway fails to shut off in response to invasive HPV skin cells, the cells continue to produce E6 and E7 proteins, multiplying in their path to becoming precancerous or cancerous. The team noted that the results reveal “a potential clinical strategy to suppress uncontrolled cell proliferation, reduce oncogene expression, and treat HPV neoplasia.”2
In their new research, following promising experiments with lab-grown skin, Ozbun and her fellow researchers conducted a proof-of-concept study in live animals harboring precancerous skin tumors. Two drugs approved by the FDA for treating some forms of cancer—cobimetinib (Cotellic; Genentech) and trametinib, which are typically administered in humans orally—were used, given that prior research has shown their effectiveness in shutting down the MEK/ERK pathway.1,3
The animals were divided into 5 groups: a control group that received a liquid with no drug; a group that received a low dose of cobimetinib; a group that received a high dose of cobimetinib; a group that received a low dose of trametinib; and a group that received a high dose of trametinib. Across all the groups, the tumors responded to the drugs; however, tumors that were treated with cobimetinib did not shrink, nor did they grow. Contrastingly, the tumors of animals treated with both doses of trametinib began to shrink 8 days following treatment initiation and were significantly smaller in size after 30 days.1,3
The oral form of trametinib is extremely toxic to both animals and people, according to Ozbun, necessitating an alternative way to get the drug to infected skin cells. Therefore, the team worked on the creation of a gel that can be absorbed through the skin of tumors, shutting down the MEK/ERK pathway. Through this approach, the gel could both kill precancerous cells and shut down HPV progression.1
“It will be the first of its kind,” Ozbun said in the article, noting that “We don’t have any antivirals for HPVs.” Given the novel formulation of trametinib, the treatment must proceed through preclinical trials to further elucidate the side effects and effectiveness of the treatment in humans. Ozbun and her team are conducting their first preclinical study by using various formulations of the gel to apply trametinib directly to skin tumors of animals, with promising initial results.1
