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Breast cancer drug shows promise to change prostate cancer treatment

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A drug used to treat breast and ovarian cancer can extend the lives of some men with prostate cancer, showed results of a major trial which could change clinical practice.

Final results from the trial showed that olaparib — a pioneering type of drug called a PARP inhibitor, a cancer drug to target an inherited genetic fault — can be used successfully to treat prostate cancers with a weakness in their ability to repair damaged DNA.

The drug was more effective than the modern hormone treatments abiraterone and enzalutamide at slowing down the growth and spread of prostate cancer in patients with advanced disease, the results showed.

The trial had already reported an improvement in disease development and outcome for this group of men with DNA repair faults in their tumours — but the final results published at this stage offer a longer follow-up and conclusively demonstrate an improvement in survival for men who were given olaparib.

The trial studied 387 men with advanced prostate cancer who had defects in one or more of 15 DNA repair genes.

Scientists at The Institute of Cancer Research (ICR), London, were the first to discover how olaparib could be targeted at tumours with faults in their ability to repair DNA.

They now expect the concluding results from the trial — presented at the European Society for Medical Oncology on Sunday and published in the journal The New England Journal of Medicine at the same time — to pave the way for regulatory approval of olaparib in prostate cancer in Europe and in the UK.

“I’m confident that our results will transform prostate cancer treatment – hopefully very soon,” said study co-leader Johann de Bono, Professor of Experimental Cancer Medicine at The Institute of Cancer Research, London.

“We have shown that olaparib, a drug already approved for use in breast and ovarian cancer, can extend the lives of men with advanced prostate who have defects in the genes BRCA1, BRCA2 or ATM and who have been treated with enzalutamide or abiraterone,” said de Bono who is also Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust.

“The FDA (Food and Drug Administration) has already approved olaparib for prostate cancer in the US and I hope that the final results of our trial will bring the authorisation of this innovative drug to Europe and the UK as soon as possible,” he said.

Men whose tumours had genetic changes were assigned to two groups: one group for those with changes in BRCA1, BRCA2 or ATM, and another group for men with genetic changes in any other of the DNA repair genes studied.

Men were then randomly assigned to olaparib or standard hormone therapy.

DNA damage is the basic cause of cancer — but it is also a key weakness of cancer that can be exploited, since cancer cells need to be able to repair their own DNA too.

In the final analysis of data from the “PROfound” trial, researchers found that olaparib blocked prostate cancer growth more effectively than the modern targeted hormone treatments abiraterone and enzalutamide in men with faulty DNA repair genes.

Patients with genetic alterations in the DNA repair genes BRCA1, BRCA2 or ATM who received olaparib had a median overall survival of 19.1 months, compared with 14.7 months for those on targeted hormone treatments, showed the results.

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Corona

Men produce more Covid antibodies than women says study

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On average, men produce more Covid-19 antibodies than women, say Portuguese researchers, adding that, 90 per cent of the patients have detectable antibodies up to seven months post contracting the SARS-CoV-2 virus.

The results, published in the European Journal of Immunology, also show that age is not a confounding factor in levels of antibodies produced, but disease severity is.

“Our immune system recognizes the virus SARS-CoV-2 as harmful and produces antibodies in response to it, which helps to fight the virus,” said study author Marc Veldhoen from Medicina Molecular Joao Lobo Antunes in Portugal.

For the findings, the research team set up an in-house sensitive specific and versatile Covid-19 serology test.

They started to monitor the antibody levels of over 300 Covid-19 hospital patients and healthcare workers, and over 200 post-Covid-19 volunteers.

The results of this six months cross-sectional study show a classic pattern with a rapid increase of antibody levels within the first three weeks after Covid-19 symptoms and, as expected, a reduction to intermediate levels thereafter.

“In this early response phase, on average men produce more antibodies than women, but levels equilibrate during the resolution phase and are similar between the sexes in the months after SARS-CoV-2 infection,” Veldhoen said.

In the acute phase of the immune response, the team observed higher antibody levels in patients with more severe disease.

Also, the results show that age is not a confounding factor for the production of antibodies, as no significant differences were observed between age groups.

Globally, 90 per cent of participants have detectable antibodies up to seven months post contracting Covid-19.

Next, the research team evaluated the function of these antibodies, i.e. their neutralizing activity against the virus SARS-CoV-2.

Also, the research team analysed the neutralizing capacity of the antibodies produced by the patients and volunteers.

“Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2,” Veldhoen said.

Importantly, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2.

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