Repurposing Cancer Drug to Prevent Organ Damage in Infectious Diseases
Twelve years ago, researchers at the University of California San Diego identified a molecule crucial for cancer cell survival by facilitating the infiltration of damaging inflammatory cells into tumor tissues. In their latest study, published in Science Translational Medicine, they reveal that this same molecule plays a similar role in lung tissue infected with COVID-19. Moreover, they demonstrate that targeting this molecule with a repurposed cancer drug could potentially mitigate organ damage in infectious diseases such as COVID-19 and methicillin-resistant Staphylococcus aureus (MRSA).
Dr. Varner explains the dual role of myeloid cells in immune response, stating, “Myeloid cells protect us, but they can also cause significant harm. During severe infections like COVID-19, excessive myeloid cell activity leads to an overproduction of inflammatory signals and destructive substances, exacerbating tissue damage.”
The molecule in question, PI3K gamma, was previously identified for its role in promoting myeloid cell migration into cancerous tissues. Building on this discovery, the researchers found that PI3K gamma also facilitates myeloid cell infiltration into tissues infected with SARS-CoV-2. This insight prompted them to investigate whether eganelisib, a PI3K gamma inhibitor used in cancer treatment, could suppress inflammation by preventing myeloid cell migration in COVID-19-infected tissues.
Using advanced sequencing techniques and bioinformatics, the team analyzed human and mouse tissue samples infected with SARS-CoV-2 to understand the cellular and molecular changes induced by the virus. Treatment with eganelisib showed promising results by effectively blocking myeloid cell entry into infected tissues, thereby potentially mitigating tissue damage caused by COVID-19. Similar positive outcomes were observed in mice infected with MRSA, underscoring the broader applicability of this approach in infectious diseases.
Dr. Varner emphasized the novelty of their approach, noting, “While other drugs tested during the early stages of the COVID-19 pandemic showed limited success, our study marks the first demonstration of targeting myeloid cells specifically through PI3K gamma inhibition as an effective strategy against COVID-19.”
Although eganelisib received FDA fast-track designation for development in 2020, it has yet to be approved for clinical use. Dr. Varner hopes that the publication of their findings will encourage pharmaceutical companies to explore the development of other PI3K gamma inhibitors for treating infectious diseases like COVID-19 and MRSA. She also underscores the importance of ongoing collaborations with infectious disease experts to further investigate and potentially validate this approach in various disease settings.
