Yale cancer researchers suggest new treatment for rare inherited cancers
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New Haven, Conn. — Studying two rare inherited cancer syndromes, Yale Cancer Center (YCC) scientists have found the cancers are driven by a breakdown in how cells repair their DNA. The discovery, published today in Nature Genetics, suggests a promising strategy for treatment with drugs recently approved for other forms of cancer, said the researchers.

The two conditions — called Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) and Succinate Dehydrogenase-related Hereditary Paraganglioma and Pheochromocytoma (SDH PGL/PCC) — boost the risk of tumors that may be benign or cancerous. Oncologists aim to remove tumors by surgery, but treatments are largely ineffective if the tumors have become metastatic.

In both inherited cancer syndromes, cells produce abnormally high amounts of metabolites, which are part of the biochemical process that the body uses to turn carbohydrates, fats, and proteins into energy. This is due to inherited defects in the genes that encode for enzymes that normally process these metabolites. The Yale investigators discovered that these high levels of metabolites can degrade a process known as homologous recombination, by which cells mend DNA damage that occurs when they divide.

“Our finding identifies an Achilles heel for these tumors, which potentially can be treated using

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