Study finds that drugs used in cancer treatments when combined with UVB light can trigger skin tumor growth!

Cancer News: The Connection Between BRAF Inhibitors and Skin Cancer
BRAF inhibitors, commonly used in cancer treatment, have proven highly effective in patients with cancers that harbor BRAFV600 mutations, particularly in melanoma. However, these targeted therapies also come with concerning side effects, one of which is the increased risk of skin cancer. Specifically, patients receiving BRAF inhibitors have been found to develop cutaneous squamous cell carcinomas (cSCCs) and other skin-related conditions. While the mechanism behind this is still under investigation, recent studies have shown a potential role of human papillomavirus (HPV) infections and exposure to ultraviolet B (UVB) light in accelerating skin tumor growth. This Cancer News report delves into a study conducted to explore the combined impact of BRAF inhibitors and UVB light on skin tumor development in mice infected with Mus musculus papillomavirus 1 (MmuPV1).


Drugs used in cancer treatments when combined with
UVB light can trigger skin tumor growth

BRAF Inhibitors and Papillomavirus: A Dangerous Duo?
The study, conducted by researchers from the Medical University of Vienna-Austria in collaboration with the U.S. National Cancer Institute, aimed to determine whether the combination of BRAF inhibitors and UVB light could synergistically enhance papillomavirus-induced skin tumors.
 
The team used a mouse model infected with MmuPV1, a virus that naturally infects mice, to mimic HPV-related skin cancer development in humans. Mice in the study were subjected to different conditions: some received BRAF inhibitors, others were exposed to UVB light, while a third group experienced a combination of both treatments. The researchers wanted to see if these treatments would accelerate the growth of skin tumors.
 
Key Findings: A Synergistic Effect on Tumor Growth
The results were striking. In the group exposed to both BRAF inhibitors and UVB light, 62% of the mice developed tumors, with tumor outgrowth becoming visible just 16 days after infection. The tumors reached an average size of 8.2 mm in length and 1.5 mm in height by the end of the study, 60 days post-infection. In contrast, mice that were either only exposed to UVB light or treated with BRAF inhibitors showed significantly lower tumor incidence, with only 20% of the UVB-exposed group developing tumors and just 5% of the BRAF inhibitor-treated group being affected.
 
Interestingly, mice that received neither treatment did not develop any tumors, emphasizing the combined effect of BRAF inhibitors and UVB light in promoting skin tumor growth. Moreover, the presence of the papillomavirus was crucial, as uninfected mice did not develop tumors, regardless of the treatments they received.
 
How BRAF Inhibitors and UVB Light Interact
BRAF inhibitors are known to paradoxically activate the MAPK pathway in cells with wild-type BRAF, leading to increased cell proliferation. In the presence of a virus like MmuPV1, w hich can induce tumor formation, this unintended activation of the MAPK pathway can lead to the rapid development of skin tumors. The researchers observed high levels of viral genome copies and spliced viral transcripts in the group exposed to both treatments, indicating that the combination of BRAF inhibitors and UVB light promoted productive viral infection and the expression of viral oncogenes.
 
In the mice exposed to both BRAF inhibitors and UVB light, there was also an increase in the expression of ERK1/2, a key protein in the MAPK pathway, further confirming that BRAF inhibitors activated this pathway. However, this effect was not observed in mice treated with UVB light alone or those infected with the virus without BRAF inhibitors, suggesting that BRAF inhibition played a central role in driving tumor growth.
 
The Role of Papillomavirus and UVB Light
One of the key aspects of this study was understanding the role of the papillomavirus in tumor development. While UVB light is a known carcinogen that can damage DNA and lead to skin cancer, its role in combination with viral infections has been less clear. The researchers found that in the presence of BRAF inhibitors, UVB light not only promoted tumor growth but also enhanced the viral infection. Mice exposed to both treatments had significantly higher levels of viral oncogene expression compared to those exposed to UVB light or BRAF inhibitors alone.
 
The study also found that the tumors in mice exposed to both treatments were enriched with viral capsid proteins, which are necessary for the assembly of new virus particles. This suggests that the combination of BRAF inhibitors and UVB light not only promotes tumor growth but also supports the persistence and spread of the virus within the skin.
 
The Importance of Genomic Stability
Another key finding of the study was the impact of UVB light and viral infection on genomic stability. UVB light is known to cause DNA damage, and the researchers observed increased expression of γH2AX, a marker of DNA double-strand breaks, in the tumors of mice exposed to UVB light and BRAF inhibitors. This increase in DNA damage likely contributed to the rapid tumor growth observed in these mice, further highlighting the dangers of combining UVB exposure with BRAF inhibitor treatment.
 
Conclusion: A Cautionary Tale for Cancer Patients
The study's findings offer important insights into the risks associated with BRAF inhibitor treatments, especially for patients who are also exposed to UVB light or have latent papillomavirus infections. The combination of these factors can significantly increase the risk of developing skin tumors, underscoring the need for careful monitoring of patients undergoing BRAF inhibitor therapy.
 
Moreover, the results highlight the importance of protecting patients from excessive UV exposure, particularly those receiving BRAF inhibitors, as UVB light can synergistically enhance the growth of papillomavirus-induced tumors. While the study was conducted in mice, its findings may have significant implications for humans, particularly for patients with melanoma or other cancers treated with BRAF inhibitors.
 
As researchers continue to explore the interactions between viral infections, cancer therapies, and environmental factors like UV light, it is crucial to develop strategies that minimize these risks. This may include better screening for viral infections in cancer patients, as well as recommendations for avoiding excessive sun exposure during treatment.
 
The study findings were published in the peer-reviewed journal: Cancers.
https://www.mdpi.com/2072-6694/16/18/3133
 
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Read Also:
https://www.thailandmedical.news/news/australia-faces-a-skin-cancer-epidemic
 
https://www.thailandmedical.news/news/pharma-news-swedish-researchers-warn-that-many-cancer-drugs-are-being-approved-despite-lack-of-proper-efficacy