Nuclear gatekeeper could block undruggable prostate cancer targets
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(PHILADELPHIA) – Certain molecular drivers of cancer growth are “undruggable” – it’s been nearly impossible to develop chemicals that would block their action and prevent cancer growth. Many of these molecules function by passing cancer-promoting information through a gate in the nucleus, where the instructions are carried out. Researchers at the Sidney Kimmel Cancer Center – Jefferson Health have found a way to block the nuclear gates used by these molecules, and show that this inhibition can halt aggressive prostate cancer in mice bearing human tumors.

The research, co-led by Veronica Rodriguez-Bravo, PhD, and Josep Domingo-Domenech, MD, PhD, published in Cell August 9, 2018.

“We found that a particular gatekeeper, the nuclear pore protein called POM121, traffics molecules that boost tumor aggressiveness,” said first and co-corresponding author Dr. Rodriguez-Bravo, Assistant Professor of Cancer Biology at Jefferson (Philadelphia University + Thomas Jefferson University). “Blocking this gatekeeper prevents several molecules from reaching their targets in the nucleus, thus decreasing tumor growth.” The researchers also showed that blocking POM121 transport helps restore chemotherapy efficacy in preclinical models of the disease.

This is the first demonstration that nuclear pore proteins may be effective anti-cancer targets for prostate cancer.

Using computational biology techniques that

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