Researchers at the University of Barcelona have made a groundbreaking discovery in the fight against cancer. After treating tumors with chemotherapy and radiotherapy, senescent cells can emerge. These cells, which do not divide and are resistant to cell death, can pose a threat to patients’ recovery. In a recent study published in the journal Cell Death and Differentiation, led by Professor Joan Montero and researcher Clara Alcon, a molecular mechanism was identified that could potentially lead to the development of strategies to eliminate these harmful senescent cells in cancer patients.
Senescent cells can survive due to various factors, including exposure to cancer treatments and the accumulation of cell damage associated with aging. These cells have the ability to regenerate tumors or accelerate aging in patients if left unchecked. Understanding the survival mechanisms of senescent cells is crucial for developing new therapeutic approaches in cancer treatment. The research team focused on melanoma cells exposed to chemotherapy or radiation to unravel the role of BCL-2 family proteins in senescent cell survival. This family of proteins plays a critical role in regulating cell death, with some promoting it and others inhibiting it.
One of the key findings of the study was the identification of BCL-XL, an anti-apoptotic protein that prevents cell death, as a crucial player in the survival of senescent cells. By inhibiting BCL-XL using specific compounds, such as A-1331852 or navitoclax, the researchers were able to induce senolytic activity, effectively killing the senescent cells. The study also revealed a reduction in HRK protein levels, which allowed BCL-XL to bind to the pro-apoptotic protein BAK, inhibiting the cell death process.
The researchers highlighted the significance of their discovery, emphasizing the potential for developing new therapies that target the molecular mechanisms behind senescent cell survival. Future studies will explore whether similar molecular processes are present in other types of tumors, such as lung cancer, and investigate the role of BCL-2 family proteins in the aging process of different organs and tissues. This groundbreaking research paves the way for innovative approaches in cancer treatment and offers hope for improved outcomes for patients.
For more information on this study, the full article can be accessed in Cell Death & Differentiation (DOI: 10.1038/s41418-024-01417-z). The University of Barcelona, where the research was conducted, continues to lead the way in advancing our understanding of cancer biology and treatment strategies.
