New Barb Inhibitors May Prevent Certain Tumors cancer research

Sue Hayward was first diagnosed with ovarian cancer in 2017. The doctors acted quickly and a hysterectomy was performed, followed by sessions of chemotherapy.

But her cancer returned within a year. “I carry a mutated version of a gene known as BRCA1 which puts me at risk for breast and ovarian cancer,” said Hayward, who works at John Radcliffe Hospital in Oxford. “It runs in families. My mother died of cancer and we assume her mother died as well.”

This time the doctors turned to a new weapon in their anti-tumor depot. After decades of research – much of it done in the UK – scientists have developed a group of drugs known as Parp inhibitors. “I had further chemotherapy and then put on a daily regimen of a type of barb inhibitor pill known as olaparib. I have been cancer-free ever since,” Hayward said. observer last week.

Nor is her story unique. Across the UK, the increasing use of Parp inhibitors has raised hopes that many individuals predisposed to certain types of familial cancers can be treated simply and effectively in the coming years. In fact, it may one day be possible to use Parp inhibitors not only to treat patients after cancers appear but to prevent them from developing at all.

“Effectively, PARP inhibitors will be used as a preventative drug to prevent certain tumors from ever developing,” said Professor Herbie Newell from Newcastle University. “We will take the fight against cancer to a new level.”

Parp is short for polyadenosine diphosphate-ribose polymerase, an enzyme found in all of our cells where it plays a key role in helping cells repair damaged DNA. Parp inhibitor acts as an antitumor therapy by blocking the cancer cell’s own Parp enzyme from doing its own repair work and thus causing its death.

“Exposing the way Barb enzyme helps cells repair themselves led to the discovery of chemicals that can disrupt this process. This was the result of decades of basic research work in biology labs across the UK and this is what led us to these new drugs,” he said. Newell.

Clinical evaluation of the first Parp inhibitors began 20 years ago, just as the funded charity Cancer Research UK (CRUK) was formed from the merger of the Imperial Cancer Research Fund and the Cancer Research Campaign. The organization has since played a major role in funding research in this area.

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

“We basically found the Achilles’ heel in cancer cells and learned how to use this information to destroy them,” said Professor Steve Jackson from the University of Cambridge. His team of researchers – supported by CRUK funding – played a key role in the discovery and development of the Parp inhibitor olaparib.

This work follows previous research in the United States and the United Kingdom that revealed two genes – breast cancer 1 and breast cancer 2 (BRCA1 and BRCA2) – that contain mutated versions that increase the carrier’s risk of a number of cancers including breast, ovarian and prostate cancer. Both can be inherited from either parent and can be spread through lineages with devastating effect.

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

“When we first developed Barb 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 we did find that there were a significant number of patients who responded in depth.”

Today, barb inhibitors are given earlier and earlier to cancer patients. “We also see that a significant portion of these patients survive long-term,” Jackson added. “One woman I know, who had late-stage cancer, started taking a Parp inhibitor nearly nine years ago and is now completely free of symptoms.”

It is this advance to the drug’s previous administration that is now encouraging scientists to consider the use of Parp inhibitors such as olaparib in a preventive role. Individuals from families affected by the mutated BRCA genes will be given these drugs before they develop cancer.

This can have great benefits. Nowadays, women from affected families sometimes choose to have mastectomy or hysterectomy to prevent the onset of breast cancer or inherited ovarian cancer. Regularly taking Parp inhibitors may prevent the need for such operations.

“However, there are side effects associated with taking these medications, and it is now a matter of ongoing research to see how we can balance the risks of those side effects with the potential benefit of preventing tumor development in the first place,” Newell added. . “This is exactly the research question that is currently being addressed.”

For her part, Sue Hayward said she felt exhausted after taking the medication. “But I got used to it. At the end of the day, I feel lucky to have access to a drug like this.”

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