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Researchers at Johns Hopkins Medicine have identified a key gene, KLF5, that appears to play a significant role in the spread of pancreatic cancer. The findings, published recently, suggest that the progression of this aggressive cancer may be more closely linked to alterations in gene function rather than new genetic mutations. This discovery could pave the way for novel therapeutic strategies targeting the mechanisms of cancer metastasis.
Pancreatic cancer remains one of the deadliest cancers, largely due to its tendency to spread rapidly and its often-late diagnosis. Understanding the underlying mechanisms driving this spread is crucial for developing more effective treatments. The study highlights the importance of epigenetic changes – modifications to DNA that don’t alter the genetic code itself, but influence gene activity – in the metastatic process. This research builds on previous function demonstrating that epigenetic alterations are frequently observed in pancreatic cancer progression, even more so than genetic mutations.
The research team discovered that KLF5 contributes to cancer spread by reprogramming how genes function within cells. Experiments revealed that KLF5 doesn’t initiate metastasis through new mutations, but by altering how DNA is packaged and chemically modified – a process known as epigenetic change. This process determines which genes are turned on or off, allowing cancer cells to acquire additional capabilities for growth and dissemination. “Epigenetic changes don’t get the appreciation they deserve as a major pathway in the development and fueling of malignant tumor growth in cancer,” explained Dr. Andrew Feinberg, a professor of medicine at Johns Hopkins, as reported by Johns Hopkins Medicine.
To pinpoint the genes most influential in cancer growth and spread, the team utilized the CRISPR gene-editing tool, effectively “switching off” various genes in pancreatic cancer cells grown in the lab. Among all the genes tested, KLF5 emerged as the most potent driver of growth in metastatic cancer cells and their invasive behavior. Further analysis of tissue samples from 13 patients with pancreatic cancer revealed that 10 of them exhibited higher levels of KLF5 activity in metastatic tumors compared to the original primary tumor.
KLF5 and Epigenetic Regulation
The study found that even subtle changes in KLF5 levels can significantly impact a cancer cell’s ability to grow, divide, and metastasize. Researchers similarly identified two other genes, NCAPD2 and MTHFD1, that KLF5 regulates in metastatic cells, but not in non-metastatic cells. These genes are known as epigenetic modifiers, meaning they control gene expression by adding chemical groups to DNA and altering its packaging. According to lead author Keena Sherman, a graduate student in the program in genetics and genomics at Johns Hopkins University, “Our study adds evidence that cancer metastasis doesn’t happen because of more mutations in the primary tumor, but because of additional epigenetic changes that enable the cancer to grow and thrive… KLF5 appears to be a master regulator driving these changes and influencing genes that control invasion and resistance to therapies.”
The findings suggest that targeting KLF5 could be a promising therapeutic strategy. Dr. Feinberg noted that new treatments aimed at KLF5 are currently under development, and it may not be necessary to completely shut down the gene to achieve positive results. This is encouraging, as complete gene inactivation can sometimes have unintended consequences.
Implications for Future Research and Treatment
This research underscores the growing understanding of the role of epigenetics in cancer development and progression. While genetic mutations have long been the focus of cancer research, epigenetic changes are increasingly recognized as equally important drivers of the disease. The identification of KLF5 as a key regulator of these epigenetic changes offers a new avenue for therapeutic intervention. Further research is needed to fully elucidate the mechanisms by which KLF5 influences gene expression and to develop targeted therapies that can effectively disrupt its activity.
The study also highlights the potential for personalized medicine approaches, where treatments are tailored to the specific epigenetic profile of a patient’s tumor. By identifying epigenetic markers like KLF5 activity, clinicians may be able to predict which patients are most likely to benefit from specific therapies.
As research continues, a deeper understanding of the interplay between genetics and epigenetics will be crucial for developing more effective strategies to combat pancreatic cancer and other aggressive malignancies. The ongoing development of KLF5-targeted therapies represents a significant step forward in this effort.
Disclaimer: This article provides informational content about medical research and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of a qualified healthcare provider for any questions you may have regarding a medical condition.
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