Stopping DNA Repair in Cancer Cells

AbbVie’s interest in PARP inhibition has its foundation in Nobel prize-winning chemistry.

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Our bodies have their own built-in toolbox, and it’s filled with proteins, enzymes and many other tools that help the body to function. One of these is PARP, a protein that plays a role in repairing faulty DNA. This same protein also was found to repair certain types of cancer cells, a finding which led researchers – at AbbVie and elsewhere – to explore PARP and the effects of blocking its function.

The foundational research into DNA repair received major acknowledgement when a trio of research scientists was recognized with the Nobel Prize in chemistry for “mechanistic studies of DNA repair” in human cells. Working independently, Tomas Lindahl, Paul Modrich and Aziz Sancar discovered how cells can repair DNA damage caused by genetic factors and copying errors that occur during cellular division, as well as mutations caused by environmental factors, such as sunlight UV radiation, cigarette smoke and other toxins.

“Understanding the ways in which DNA repairs itself is fundamental to our understanding of inherited genetic disorders and of diseases like cancer,” said Sir Martyn Poliakoff, vice president of the U.K.’s Royal Society, at the Nobel announcement.

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PARPs are nuclear enzymes important in DNA repair.

Targeting PARP

In recent years, AbbVie’s oncology researchers have been building on the insights yielded by Lindahl, Modrich and Sancar to develop new targeted therapies for cancer patients.

“All living organisms routinely experience damage to their DNA, and cells are constantly repairing it so that the organisms don’t die. In most cancers, some of the cell’s DNA repair mechanisms have been deactivated,” says Vincent Giranda, M.D., Ph.D., oncology project director at AbbVie. “This Nobel-winning research has helped us better understand why DNA damage is important, both in the genesis of cancer and in the therapies used to treat it.”

Because PARP is known to play an important role in DNA repair, the idea is that inhibiting the PARP enzyme might help prevent DNA repair in cancer cells. And if cancer cells lose their ability to repair, common DNA-damaging therapies like chemotherapy or radiation that target those cells may potentially increase their effectiveness.

“At some point during treatment, almost everyone who has advanced cancer gets some type of DNA-damaging therapy. These foundational ideas about the molecular basis for DNA repair have taken us to focus our research on the next generation of DNA-repair inhibitors, which we ultimately hope will provide physicians and patients with new cancer treatments,” says Dr. Giranda.

Learn more about the 2015 Nobel Prize in Chemistry laureates and their groundbreaking research.

Learn more about AbbVie’s oncology pipeline.

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Elizabeth Hoff
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