Discoveries Reveal Key Factors in the Development of Basal Cell Carcinoma
An international collaboration has shed light on the crucial role of a protein known as Survivin in the initiation and progression of basal cell carcinoma, the most prevalent form of skin cancer among humans. This groundbreaking research, published in the journal Cancer Discovery, was spearheaded by a team from the Champalimaud Foundation in Lisbon, Portugal.
Basal cell carcinoma is recognized for its high incidence rates, with many individuals either personally affected or knowing someone who has encountered this condition. While it typically does not spread to other parts of the body and is often managed through simple surgical procedures, there are instances where it can become aggressive or metastatic. Understanding the mechanisms underlying its development is therefore critical.
The research builds upon previous findings from 2016, where investigators identified that skin stem cells are the primary contributors to basal cell carcinoma, as opposed to progenitor cells, which are their immediate descendants. This prompted further inquiries into the differences in cancer initiation capabilities between these two cell types.
To explore this, the researchers conducted transcriptional profiling in animal models, examining the gene expressions of oncogene-activated skin stem cells versus skin progenitor cells. This analysis led them to identify several upregulated genes, with Survivin (also referred to as BIRC5) standing out as a significant factor.
Survivin is known for its anti-apoptotic properties, aiding in cell survival during division. The researchers investigated whether the expression of Survivin in activated stem cells contributed to their survival and proliferation, ultimately resulting in the formation of basal cell carcinoma.
In a series of experiments, the team deleted the Survivin gene from their genetically modified mouse models post-activation of oncogenes. The results confirmed their hypothesis; the absence of Survivin rendered stem cells incapable of tumor formation. Conversely, they discovered that by overexpressing Survivin in progenitor cells, these cells could also initiate tumors, demonstrating that this protein can convert non-cancerous cells into cancer-competent cells.
Further investigations revealed that inhibiting Survivin in preneoplastic lesions not only halted their progression into invasive tumors but also indicated its essential role in both the initiation of cancer and the transition of preneoplastic lesions to malignant states. This finding is pivotal, as it opens the door to potential therapeutic strategies targeting Survivin.
Currently, several Survivin inhibitors are undergoing clinical trials, and initial data suggests that short-term application of these inhibitors can reduce preneoplastic lesion sizes and thwart the progression of basal cell carcinoma. However, toxicity issues with these inhibitors in animal models prompted researchers to consider alternatives.
As a result, they explored the use of inhibitors targeting a protein known as SGK1 (serum and glucocorticoid-regulated kinase 1), which also proved effective in preventing the advancement of preneoplastic lesions into tumors. The research team noted that SGK1 inhibitors have shown promise in various cancer types, suggesting a viable approach for therapy in human patients.
The implications of these findings are considerable, as they provide a pathway toward preventing invasive basal cell carcinomas and highlight the potential for topical application of Survivin inhibitors, which could minimize side effects compared to systemic treatments.
In summary, the discovery that Survivin not only supports tumor growth but can also convert resistant cells into cancer-initiating cells marks a significant advancement in understanding basal cell carcinoma. This knowledge lays the groundwork for future research and potential treatments aimed at combating this widespread cancer.
No comments yet. Be the first to comment!