At the Lab Ep. 24: Putting the brakes on brain cancer

TL;DR

Discovery of BRD8's role in glioblastoma offers new treatment path.

Transcript

[music] You’re now At the Lab with Cold Spring Harbor Laboratory. I’m Sara Giarnieri, and this week At the Lab, “Putting the brakes on brain cancer.” [A car drives along.] If the cells in your body are like cars on the road, then the P53 protein would be akin to the car’s brakes. [Suddenly, the car comes screeching to a halt.] It helps to slow c... Read More

Key Insights

• Professor Alea Mills' research focuses on the role of P53 in glioblastoma, a deadly brain cancer, comparing it to car brakes.
• P53 mutations are common in many cancers but not in glioblastoma, prompting a search for other mechanisms affecting P53.
• Mills' team explored epigenetic factors, which do not alter DNA sequences but influence gene expression, to find glioblastoma vulnerabilities.
• The research utilized CRISPR technology from CSHL Professor Christopher Vakoc's team to identify proteins involved in cancer progression.
• The team discovered that BRD8 protein is responsible for inhibiting P53 in glioblastoma, effectively cutting the 'brakes' on cell growth control.
• Targeting BRD8 can restore P53 function, inhibiting tumor growth in lab and mouse models, offering a potential new treatment strategy.
• The study highlights the importance of epigenetic research in understanding and treating cancers that do not involve genetic mutations.
• The discovery is a significant step forward in the potential development of drugs targeting BRD8 to treat glioblastoma.

Questions & Answers

Q: What is the significance of P53 in cancer research?

P53 is a crucial protein that acts as a tumor suppressor by regulating cell division and preventing cells from growing uncontrollably. Mutations in the gene that produces P53 are among the most common genetic causes of cancer, making it a significant focus in cancer research. Understanding how P53 functions and is regulated can lead to new therapeutic strategies for various cancers.

Q: Why is glioblastoma challenging to treat compared to other cancers?

Glioblastoma is challenging to treat because it often does not involve common genetic mutations like those in the P53 gene. Instead, it may involve epigenetic changes that affect gene expression without altering the DNA sequence. This makes it difficult to target with traditional genetic-based therapies, necessitating new approaches to identify and target the underlying mechanisms driving the cancer.

Q: How did the Mills lab utilize CRISPR technology in their research?

The Mills lab used CRISPR technology, developed by CSHL Professor Christopher Vakoc's team, to screen for proteins involved in cancer progression. CRISPR allows researchers to precisely edit genes and study their functions, helping identify BRD8 as a protein that inhibits P53 in glioblastoma. This discovery was crucial in understanding how glioblastoma cells evade growth control and in developing potential new treatments.

Q: What role does BRD8 play in glioblastoma?

BRD8 is a protein identified by the Mills lab as a key player in inhibiting the tumor suppressor function of P53 in glioblastoma. By effectively 'cutting the brakes' on P53, BRD8 allows glioblastoma cells to grow uncontrollably. Targeting BRD8 can restore P53's function, offering a potential therapeutic approach to control glioblastoma growth.

Q: What is the potential impact of targeting BRD8 in glioblastoma treatment?

Targeting BRD8 in glioblastoma has the potential to restore the tumor suppressor function of P53, effectively 'reconnecting the brakes' on cell growth. This could inhibit tumor growth and provide a new treatment strategy for glioblastoma, which is notoriously difficult to treat due to its complex biology. This approach highlights the importance of epigenetic research in developing cancer therapies.

Q: How does epigenetic research differ from genetic research in cancer?

Epigenetic research focuses on changes that affect gene expression without altering the underlying DNA sequence, while genetic research typically involves studying mutations within the DNA. Epigenetic changes can be reversible and are influenced by environmental factors, making them a promising target for cancer therapies, especially in cancers like glioblastoma that do not involve common genetic mutations.

Q: What challenges exist in developing drugs targeting BRD8?

Developing drugs targeting BRD8 involves several challenges, including ensuring specificity to avoid off-target effects, determining the optimal method of delivery, and understanding the potential side effects. Additionally, the drug development process requires extensive testing in preclinical and clinical trials to establish safety and efficacy, which can be time-consuming and costly.

Q: What are the next steps in the research following the discovery of BRD8's role in glioblastoma?

Following the discovery of BRD8's role in glioblastoma, the next steps include developing specific inhibitors of BRD8, testing their efficacy in preclinical models, and eventually conducting clinical trials to evaluate their safety and effectiveness in humans. Further research is also needed to understand the broader implications of targeting epigenetic factors in cancer treatment and to explore potential combination therapies.

Summary & Key Takeaways

• Professor Alea Mills and her team at Cold Spring Harbor Laboratory are investigating glioblastoma, a deadly brain cancer, by focusing on the P53 protein. Unlike many cancers, glioblastoma does not typically involve mutations in P53, prompting a search for other mechanisms affecting its function.

• The research team explored epigenetic factors, which influence gene expression without altering DNA sequences, to find vulnerabilities in glioblastoma. Utilizing CRISPR technology developed by CSHL Professor Christopher Vakoc, they identified BRD8 as a key protein inhibiting P53 in glioblastoma.

• Targeting BRD8 can restore the function of P53, effectively 'reconnecting the brakes' on cell growth. This breakthrough offers a promising new treatment strategy for glioblastoma, highlighting the potential of epigenetic research in developing cancer therapies.