New ‘Parp inhibitors’ may prevent certain tumors from occurring |  Cancer research

New ‘Parp inhibitors’ may prevent certain tumors from occurring | Cancer research

Sue Hayward was first diagnosed with ovarian cancer in 2017. Doctors acted quickly and she was given a hysterectomy followed by sessions of chemotherapy.

But her cancer returned within a year. “I have a mutated version of a gene known as BRCA1 which makes me susceptible to breast and ovarian cancer,” said Hayward, who works at the John Radcliffe Hospital, Oxford. “It runs in families. My mother died of cancer and we assume her mother did too.”

This time, doctors turned to a new weapon in their anti-tumor arsenal. After decades of research – much of it carried out in the UK – scientists have developed a series of drugs known as Parp inhibitors. “I had more chemotherapy and then was put on a daily regimen of a brand of Parp inhibitor pill known as olaparib. I’ve been cancer free ever since,” Hayward said Observer last week.

Her story is not unique either. Across the UK, increasing use of Parp inhibitors has raised hopes that many individuals susceptible to certain familial cancers could be treated easily and effectively in the coming years. Indeed, it may one day be possible to use Parp inhibitors not only to treat patients after cancer has appeared, but to prevent it from developing at all.

“Parp inhibitors would effectively be used as a preventative medicine to stop certain tumors from ever appearing,” said Newcastle University Professor Herbie Newell. “We will have moved the fight against cancer to a new footing.”

Parp is short for polyadenosine diphosphate-ribose polymerase, an enzyme found in all our cells where it plays a key role in helping cells repair damaged DNA. A Parp inhibitor works as an anti-tumor treatment by stopping a cancer cell’s own Parp enzyme from doing its repair work and causing it to die.

“Discovering the way the Parp enzyme helps cells repair themselves led to the discovery of chemicals that can interfere with this process. This was the result of decades of basic research work in biology laboratories across the UK and is what has led us to these new medicines, said Newell.

The clinical evaluation of the first Parp inhibitors began 20 years ago, just as the funding charity Cancer Research UK (CRUK) was formed from a merger of the Imperial Cancer Research Fund and the Cancer Research Campaign. Since then, the organization has played a key role in funding research in the field.

Sue Hayward with her husband, Kieran, in the Lake District.
Sue Hayward with her husband, Kieran, in the Lake District. Photo: Sent by her

“Essentially, we have found the Achilles heel of tumor cells and have learned how to use this information to destroy them,” said cancer expert Prof. Steve Jackson of Cambridge University. His team of researchers – supported by CRUK funding – played a key role in the discovery and development of the Parp inhibitor olaparib.

This work followed earlier research in the US and UK which had revealed the existence of two genes – breast cancer 1 and breast cancer 2 (BRCA1 and BRCA2 gene) – which have mutated versions that increase a carrier’s risk of developing a range of cancers, including in the breast, ovary and prostate. Each can be inherited from both parents and can be spread through families with devastating effect.

It is estimated that in the UK there are tens of thousands of people who carry pathogenic versions of the BRCA1 and BRCA 2 genes. For these individuals, the development of Parp inhibitors offers the prospect of protection against the increased cancer risk that they have inherited.

“When we first developed Parp inhibitors, we gave them to patients who were in the late stages of cancer,” Jackson said. “They had nothing to lose. We weren’t sure what to expect, but found that there were quite a few patients who responded quite profoundly.”

Today, Parp inhibitors are being given earlier and earlier to cancer patients. “We also see that a significant proportion of these patients survive long-term,” Jackson added. “A lady I know, who had late-stage cancer, started taking a Parp inhibitor almost nine years ago and is now completely symptom-free.”

And it is this progression to earlier administration of the drug that is now encouraging researchers to consider the use of Parp inhibitors such as olaparib in a preventive role. People from families affected by mutated BRCA genes will receive these drugs before they had developed cancer.

This can have significant benefits. Currently, women from affected families sometimes choose to have a mastectomy or hysterectomy to prevent the onset of hereditary breast or ovarian cancer. Regular use of Parp inhibitors may prevent the need for such operations.

“But there are side effects involved in taking these medications, and it is now a matter of ongoing research to find out how we can balance the risk of these side effects with the potential benefit of preventing tumor development in the first place,” Newell added. . “That is exactly the research question that is now being addressed.”

For her part, Sue Hayward said she had felt tired after taking the drug. “But I’ve gotten used to it. At the end of the day, I just feel lucky to have had access to a medicine like this.”

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