Exploring the Molecular Basis of VHL – Tumor Heterogeneity in VHL ccRCC | Medical Symposium 2024 скачать в хорошем качестве

Exploring the Molecular Basis of VHL – Tumor Heterogeneity in VHL ccRCC | Medical Symposium 2024

In this informative session, the speakers explore the molecular bases of Von Hippel-Lindau (VHL) disease, highlighting the influence specific genetic mutations can have on tumor growth. Speaker #1: Dr. Tom Mitchell discusses the challenges in managing tumor growth in patients with VHL disease, highlighting the unpredictable nature of tumor growth rates—some tumors grow rapidly, while others remain stable or shrink. Mitchell's research focuses on the tumor microenvironment, specifically the area where tumor cells intersect with normal kidney tissue. He discovered that certain immune cells, specifically macrophages producing a molecule called IL-1 beta, accumulate in this region and promote aggressive tumor behavior by encouraging cancer cells to become more invasive. Dr. Mitchell proposes that blocking IL-1 beta may help to slow tumor growth. Speaker #2: Dr. Isaline Rowe discusses her study on tumor diversity in VHL patients. She explains that patients can develop multiple kidney tumors that behave differently, even within the same patient or family, complicating treatment strategies. Her team analyzed several tumors from a single VHL patient, taking multiple biopsies from different regions of each tumor. Despite differences in imaging characteristics, all tumors exhibited a specific chromosomal alteration known as 3p loss. However, each kidney tumor showed a different degree of 3p loss, suggesting they develop independently. Understanding these underlying factors is crucial for understanding why all VHL-related tumors do not respond to belzutifan treatment. Speaker #3: Dr. Samra Turajlic explores the concept of tumor evolution in VHL disease. She discusses how tumors evolve over time through genetic changes, beginning with the loss of the VHL gene located on chromosome 3p. Her study finds that tumors within the same VHL patient can follow different genetic pathways, leading to variability in tumor behavior and treatment response. Dr. Turajlic notes that certain genetic changes, like the loss of specific chromosomal regions such as 9p and 14q, are linked to more aggressive tumors that are likely to spread. Her work highlights how mapping these evolutionary trajectories of tumor cells is important for helping predict which tumors might become dangerous, allowing doctors to tailor treatment plans accordingly. Speaker #4: Francesca Cuomo presents her research on gender differences in tumor development. She investigates why clear cell renal cell carcinoma (ccRCC) occurs more frequently in men than in women, focusing on specific genes that may explain this disparity. The key genes studied include VHL, PBRM1, and KDM5C, which, when lost, can lead to cancer development. The KDM5C gene is located on the X chromosome, meaning that in humans, males only have 1 copy of this gene, whereas females have 2 copies. In mouse models engineered to lack all three genes (VHL, PBRM1, and KDM5C), both male and female mice developed kidney cancer, but female mice exhibited more tumors than males. These findings suggest that the KDM5C gene may be partly responsible for the higher frequency of ccRCC in males versus females. She then highlights that the combined loss of the three genes leads to DNA replication problems and genetic mutations that favor cancer formation. Understanding how these genetic differences between males and females influence tumor development can lead to better prevention strategies and treatments that consider both genetic makeup and gender.