November 1, 2014

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

Volume II, Autum 2005

 

Unleashing Good Genes to Reform Cancer Cells


Imagine a garden hose, neatly wrapped around a coil. It may be the greatest hose in the world, but while it’s all rolled up like that, it can’t do much to help your flowers.

A similar situation exists in prostate cancer, and oncologist Roberto Pili, M.D., assistant professor of oncology, believes unwrapping a specific piece of DNA — the gardenhose, on a molecular level — can stop the transformation of a normal cell into a cancerous one. In fact, it may even cause a cancerous cell to revert back to its harmless state.

Pili has been named The Peter Jay Sharp Foundation scholar from The Patrick C.Walsh Prostate Cancer Research Fund. He is focusing on a tiny site, found in every cell that has a nucleus, called chromatin. Chromatin contains spool-shaped proteins called histones. But here’s the interesting twist: In this peculiarly structured area, DNA wraps itself in a big bear hug around the histones —think of filet mignon, bundled in two strips of bacon — and keeps them tightly coiled. This wrapping silences the proteins, keeping these particular genes turned off, or asleep.

Sometimes this is a bad thing — particularly when there’s trouble afoot, when normal cells are changing, and encouraging cancer.When good cells go bad, they lose their well-differentiated (distinct, or clearly defined) structure and normal regulation routines, and melt together. They encourage the growth of blood vessels that can supply newlife to a tumor. Pili believes that waking up the sleeping genes — in this case, in epithelial cells, which make up the prostate’s glandular tissue — will counteract the loss of certain key proteins that can help cancer thrive.

“If we can reactivate these specific proteins in the tumor,” Pili says, “we can push cancer cells to differentiate — to turn back into regular cells — and eventually, to die. ”Pili is testing drugs known to act on the chromatin, called histone deacetylase inhibitors, and he’s hoping for a double impact: He wants to wake up some goodgenes, and cause some cancer-promoting genes to be repressed.

If these drugs pack the punch Pili believes they will — if they teach a cancer cell to change its ways — he envisions one day using them in combination with other therapies for men with metastatic prostate cancer.“This study represents a novel and exciting approach toward conquering prostate cancer,” he says, “by using agents that push tumor cells to return to normal epithelium.”

 

 

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