Researchers at MSK have made a groundbreaking discovery linking chromosomal instability and epigenetic changes in cancer, particularly in advanced drug-resistant forms. These defects collaborate to create variations among cancer cells within the same tumor, enhancing their survival and resistance to treatment. The newfound connection not only opens up potential new treatment avenues but also presents vast new areas for exploration and research.
A graduate student’s curiosity led to the identification of this previously unknown relationship between two critical cancer hallmarks: chromosomal instability and epigenetic alterations.
The research, published in Nature, not only provides a promising foundation for biological research but also holds clinical significance.
Chromosomal instability refers to changes in the number of chromosomes in cancer cells. Epigenetic alterations, on the other hand, modify gene expression without changing the cell’s DNA code.
The student, Albert Agustinus, working under Dr. Samuel Bakhoum at MSK, explored the link between chromosomal instability and epigenetic modifications. The surprising finding of this collaboration with Dr. Yael David’s lab revealed that ongoing chromosomal instability contributes to epigenetic abnormalities, even without mutations in the genes that encode epigenetic-modifying enzymes.
The presence of micronuclei, small extra nuclei in cells, indicates chromosomal instability and disruption of chromatin organization, leading to ongoing epigenetic dysregulation. The accumulation of epigenetic changes among individual cancer cells within a tumor makes some cells resistant to treatment, fueling cancer progression.
The researchers used sophisticated experiments to analyze epigenetic changes inside the cells, offering insights into the transcription of important genes in specific pathways.
The study has significant clinical implications. Epigenetic changes are reversible, and drugs targeting them have already been developed. Chromosomal instability and the presence of micronuclei might serve as biomarkers to identify patients who can benefit from epigenetic modifying therapies. Additionally, combining efforts to target chromosomal instability directly with suppressing epigenetic alterations could lead to more effective therapeutic approaches.
The research also suggests exploring methods to prevent micronuclei from rupturing, as this is a major driver of epigenetic changes.
Overall, this discovery holds great promise for advancing cancer treatment by providing a deeper understanding of the relationship between chromosomal instability and epigenetic alterations and facilitating targeted therapeutic approaches.
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Frequently Asked Questions (FAQs) about cancer hallmarks
What did the scientists discover in their research?
The scientists discovered a surprising link between two key cancer hallmarks: chromosomal instability and epigenetic changes. These defects work together to create variations among individual cancer cells within the same tumor, making them more resistant to treatment.
How do chromosomal instability and epigenetic changes relate to cancer?
Chromosomal instability involves changes in the number of chromosomes in cancer cells, while epigenetic changes modify gene expression without altering the DNA code. The research revealed that ongoing chromosomal instability leads to epigenetic abnormalities, even without mutations in the genes that encode epigenetic-modifying enzymes.
Micronuclei are small, extra nuclei in cells that indicate chromosomal instability. In cancer, they disrupt chromatin organization, leading to ongoing epigenetic dysregulation and the accumulation of epigenetic changes among individual cancer cells.
What are the clinical implications of this research?
The findings have significant clinical implications. Epigenetic changes are reversible, and there are already drugs targeting them. Chromosomal instability and the presence of micronuclei might serve as biomarkers to identify patients who can benefit from epigenetic modifying therapies. The research also suggests combining efforts to target chromosomal instability with suppressing epigenetic alterations for more effective therapeutic approaches.
How might this research impact cancer treatment?
The discovery of the link between chromosomal instability and epigenetic changes provides a deeper understanding of cancer progression and treatment resistance. It offers new avenues for targeted therapies, potentially improving cancer treatment outcomes and patient survival.
More about cancer hallmarks
- Nature: “Epigenetic dysregulation from chromosomal transit in micronuclei” (Link: https://www.nature.com/articles/s41586-023-06084-7)
- Nature: “Heritable transcriptional defects from aberrations of nuclear architecture” (Link: https://www.nature.com/articles/s41586-023-06157-7)
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