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Deciphering the Mystery of Epigenetic Drugs Resistance in Cancer Treatment

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Ethan Sulliva
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Deciphering the Mystery of Epigenetic Drugs Resistance in Cancer Treatment

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Understanding Epigenetics in Cancer

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Epigenetics, the study of changes in organisms caused by modification of gene expression, has emerged as a critical field in understanding cancer. Alterations in epigenetics have become a key feature of human tumors and led to the development of nine epigenetic drugs for use in oncology. These drugs, designed to alter genetic expression without changing the DNA sequence itself, reprogram cancer cells to behave like normal cells, opening a promising avenue for cancer treatment.

The Mystery of Drug Resistance

Despite the potential of epigenetic drugs, a perplexing mystery has remained. Some patients respond remarkably well to these drugs, while others show resistance. A study led by Dr. Manel Esteller recently provided the first answer to this question. The study focused on myelodysplastic syndrome (MDS), a type of cancer that affects the blood and bone marrow, and the use of the epigenetic drug azacitidine.

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The Role of Mutations in Drug Resistance

The study discovered that the persistence of certain single cancer cells with mutations is associated with the lack of clinical benefit from these drugs. Patients who respond to treatment show a decrease in the number of mutations in stem and progenitor cells. This suggests that eliminating these altered primitive cells is crucial for the success of therapy. Additionally, the study identifies new mutations that may be targets of other drugs, offering hope for patients resistant to epigenetic drugs. In essence, molecular studies at the single cell level can predict not only the prognosis of the disease but also its sensitivity to different treatments.

Overcoming Resistance with Combination Therapy

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A team led by physician scientist Dr Alex Kentsis designed a combination therapy that overcomes resistance to tazemetostat, a drug used to treat epithelioid sarcomas and rhabdoid tumors. This combination therapy uses an epigenetic treatment strategy to alter the expression of genes. The researchers tested this therapy using tazemetostat together with an experimental drug called barasertib, which slowed tumor growth in mice, suggesting the treatment approach is promising.

Epigenetics in Leukemia and Beyond

Similar findings were reported in leukemia patients, where the persistence of certain single cancer cells with mutations impacted the response to epigenetic drugs. In both breast and prostate cancer, understanding the role of enzymes that modify histone proteins and the relationship between epigenetic modifications and the tumor microenvironment has proven critical to advancing therapeutic strategies.

The Future of Epigenetic Therapy

The current research in the field of epigenetics has opened up new avenues of treatment and offers hope for more effective cancer therapy. By understanding the role of mutations in drug resistance, scientists can design more effective treatments and predict patient outcomes more accurately. The ongoing research in this field is promising, and the future of cancer treatment could see significant advances as our understanding of epigenetics deepens.

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