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Radiation-Resistant Cancer Cells Can Be Killed Using Drug That Coaxes Persistent p53 Signaling
February 17, 2021
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All tissues are not equally sensitive to radiation. It has long been recognized that the well-known tumor suppressor protein and transcription factor p53 is linked to the degree of a tissue’s sensitivity to radiation. Yet how p53 regulates vulnerability to radiation has been elusive so far.
In an article titled “
Nature Communications, scientists at the Blavatnik Institute at Harvard Medical School, Massachusetts General Hospital, and the Novartis Institutes for BioMedical Research clarify that it is not the abundance of p53 protein in a tissue’s that correlates with the tissues’ sensitivity to radiation but the dynamics of p53 signaling following radiation.
Cellular survival after radiation exposure depends on the specific protein behavior
Exposure to radiation can wreak indiscriminate havoc on cells, tissues, and organs. Curiously, however, some tissues are more vulnerable to radiation damage than others.
Scientists have known these differences involve the protein p53, a well-studied tumor-suppressor protein that initiates a cell s auto-destruct programs. Yet, levels of this sentinel protein are often similar in tissues with vastly different sensitivities to radiation, posing the question: How is p53 involved?
A new study by researchers in the Blavatnik Institute at Harvard Medical School, Massachusetts General Hospital, and the Novartis Institutes for BioMedical Research now sheds light on this mystery.
Reporting in
Nature Communications on Feb. 9, they describe how cellular survival after radiation exposure depends on behavior of p53 over time. In vulnerable tissues, p53 levels go up and remain high, leading to cell death. In tissues that tend to survive radiation damage, p53 levels oscillate up and down.
“Dynamics matter. How things change over time matters,” said co-corresponding author Galit Lahav, the Novartis Professor of Systems Biology at HMS. “Our ability to understand biology is limited when we only look at snapshots. By seeing how things evolve temporally, we gain much richer information that can be critical for dissecting diseases and creating new therapies.”
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