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Preclinical study explores approved drug for ovarian cancer

Treatment with the iron-binding drug deferiprone elicits a natural killer cell response in a preclinical model of ovarian cancer

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An iron-binding drug that is already approved for the treatment of other diseases could provide a novel way to attack ovarian tumours, new research has shown.

Iron is essential for multiple cellular processes, so actively multiplying cancer cells often need larger amounts of it than normal cells. That’s especially true in ovarian cancers.

The preclinical study, led by Weill Cornell Medicine researchers, looked at the iron-binding drug deferiprone and combined the analysis of human ovarian tumours and animal models of the disease. Iron-chelating drugs bind tightly to iron, preventing cells from using it.

“We thought that was a perfect opportunity to try a new approach, because deferiprone has been successfully used for other diseases with abnormal iron accumulation,” said senior author Dr Juan Cubillos-Ruiz, distinguished associate professor for infection and immunology in obstetrics and gynaecology at Weill Cornell Medicine.

To confirm the importance of iron in ovarian cancer, Dr Cubillos-Ruiz’s team first looked at a collection of human tumour samples they have amassed over the past decade and analysed public genomic datasets from ovarian cancer patients.

“We can isolate different components of tumours from ovarian cancer patients, and study their molecular processes,” Cubillos-Ruiz explained.

The scientists found that ovarian cancer cells demonstrate increased expression of iron-related genes, which correlated with poor patient prognosis. The investigators also found that fluid surrounding ovarian tumours contain high iron content that is readily available to cancer cells.

The researchers next looked at animal models of the disease.

“We have advanced mouse models of metastatic ovarian cancer that are immunocompetent, so this allows us to study the immune system response in the disease, which is a crucial component,” Dr Cubillos-Ruiz said.

Previous iron-related studies have used mice with compromised immune systems, precluding the understanding of how different therapies affect immune responses to tumours.

The investigators found that the mice recapitulated the disease features quite well: as ovarian cancer progressed, there was more iron accumulation in the tumour, and the cancer cells selectively over-expressed the iron-related gene signatures.

In the animals, deferiprone treatment worked even better than cisplatin, the current standard for ovarian cancer chemotherapy, and functioned directly inside the cells.

“We demonstrated that deferiprone can chelate iron in ovarian cancer cells, in vivo” said lead author Dr Tito Sandoval, a former postdoctoral fellow in Dr Cubillos-Ruiz’s lab.

“We found that combining cisplatin and deferiprone markedly extended the survival of mice with metastatic ovarian cancer, working synergistically compared with the monotherapies. So, we decided to identify the mechanisms behind this effect.”

The team found that by starving cancer cells of iron, deferiprone triggers a cellular stress response, which prompts the immune system to attack them. Cisplatin affects cancer cell DNA replication, so the two drugs appear to be complementary.

Dr Cubillos-Ruiz is now working with clinical collaborators to design human trials of the new approach.

Though deferiprone is already approved for treating other conditions, he emphasised that the team still needs to determine the best way to use it against ovarian cancer.

“We want to maximise the potential therapeutic effects, so the clinical trial design is critical,” he added.

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Diagnosis

AI may help accelerate breast cancer diagnosis for high-risk women – study

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AI may help speed breast cancer diagnosis for high-risk women after abnormal mammograms, a study suggests.

Women with abnormal mammograms often wait weeks to learn whether they have breast cancer.

Researchers at UC San Francisco and UC Berkeley said an AI-guided workflow could help reduce that wait by quickly identifying those most likely to have the disease. Some women could move from imaging to evaluation, and sometimes biopsy, in a single day.

Dr Maggie Chung, first author of the study, said: “This is a really an exciting time.

“This moves us closer to personalised care, where we can tailor a plan so that each patient gets the right intervention at the right time.”

The study used an open-source AI model called Mirai.

The model was trained on hundreds of thousands of mammograms linked to patients’ cancer outcomes.

A mammogram is an X-ray scan of the breast used to look for signs of cancer. A biopsy involves taking a small tissue sample to test for disease.

The AI tool is designed to detect subtle patterns in screening mammograms and predict a woman’s cancer risk.

Researchers at UC San Francisco and UC Berkeley applied the model to more than 4,100 screening mammograms at Zuckerberg San Francisco General Hospital and Trauma Center.

Mirai identified 525 women, about 12.7 per cent of screened patients, as high risk.

Those patients could receive an interpretation of their mammograms immediately after the scan and have additional diagnostic imaging for suspicious areas on the same day.

Some women who needed biopsies were also able to have them on the same day.

The researchers said Mirai reduced the wait time for diagnostic evaluation from several weeks to about an hour.

For women who were ultimately diagnosed with breast cancer, it reduced the average wait for biopsy from more than two months to fewer than 10 days.

The researchers stressed that Mirai does not replace radiologists or make diagnoses on its own.

Instead, it acts as a triage tool to help physicians identify the patients who can benefit most from accelerated care.

The team analysed more than 114,000 archival mammograms before launching the programme, to ensure the model would capture enough high-risk patients without overloading the clinic with too many expedited evaluations.

The researchers said they hope AI will support a more personalised approach to breast cancer screening tailored to each patient’s breast cancer risk.

Chung said: “Right now, many women follow the same screening schedule but their individual risk can be very different.

“AI risk assessment gives us the chance to identify the women most likely to benefit from expedited care and get them what they need.”

Adam Yala, senior author of the study and a data scientist at UC Berkeley, said: “This is a powerful example of how AI can be a collaborative partner for physicians.

“It shows how we can improve care when we bring clinicians and data scientists together to design these systems.”

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Fertility

Infertility may be risk factor for early menopause, study suggests

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Women with primary infertility may face a higher risk of early menopause and reach it about a year earlier, a study suggests.

The findings suggest women with primary infertility may be more likely to enter menopause before the age of 45.

The increased risk appeared most notable among women with unexplained infertility or a history of endometriosis.

Dr Stephanie Faubion, medical director for The Menopause Society, said: “This study shows that women with primary infertility, specifically those with unexplained infertility or a history of endometriosis, were at risk for early menopause.

“Given that early menopause is linked to adverse long-term health consequences, these women may benefit from counselling that they are at risk of early menopause.

“This will allow them to monitor for early menopause and to seek treatment with hormone therapy, if indicated.”

Early menopause is usually defined as menopause before age 45, while premature menopause is menopause before age 40.

Women who experience menopause earlier may face symptoms for longer and have a higher risk of long-term health problems.

These can include cardiovascular disease, osteoporosis and neurocognitive disorders. Osteoporosis weakens bones, while neurocognitive disorders affect memory, thinking or brain function.

The study, highlighted by The Menopause Society, involved nearly 700 people, roughly half of whom had been diagnosed with primary infertility.

It found that women with a history of primary infertility underwent natural menopause about one year earlier than those without such a history.

Researchers found no association between infertility and premature menopause.

Infertility affects around one in six people globally and can have consequences beyond family planning.

Previous research has linked infertility with higher rates of cancer and cardiovascular disease, although causes vary and may involve genetic, hormonal, in-utero or lifestyle factors.

In-utero factors are influences that occur while a baby is developing in the womb.

Earlier studies looking at links between infertility and early or premature menopause have produced mixed results, with some not accounting for different types of infertility.

The new study suggested that women with unexplained infertility or a history of endometriosis may have an increased risk of early menopause.

Endometriosis is a condition where tissue similar to the lining of the womb grows elsewhere in the body. It can cause pain, heavy periods and fertility problems.

Known risk factors for early or premature menopause include tobacco use, low body mass index, not having given birth and starting periods at a younger age.

Women who have had more childbirths and those with a history of oral contraceptive use have previously been linked to later menopause.

The researchers said women with primary infertility may benefit from additional counselling because of the systemic and long-term health effects of early menopause.

They also said women should be encouraged to seek evaluation and treatment if they experience a new loss of menstrual cycles.

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pain conditions

Endometriosis documentary profiles stars including Marilyn Monroe and Amy Schumer

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A non-profit has launched an endometriosis documentary featuring Amy Schumer and Marilyn Monroe as it pushes for changes in how the condition is treated and understood.

The Endometriosis Collective has launched to change how endometriosis is researched, treated and understood, starting with a documentary featuring stories from people including Amy Schumer and Marilyn Monroe.

The feature-length documentary, “End of the Cycle”, will premiere in New York on Tuesday, and The Endometriosis Collective is making the film free to stream online.

Schumer, a comedian, writer and actor, has previously spoken of how endometriosis left her “on the floor in pain, vomiting from the pain, the pain that nobody can see.”

Schumer is one of several celebrities featured in the documentary. Other contributors include dancer Julianne Hough, Olympic medallist Brittany Brown and actors Janel Parrish and Folake Olowofoyeku.

The Endometriosis Collective timed the documentary premiere to coincide with the 100th anniversary of Marilyn Monroe’s birth.

Monroe, who died in 1962, starred in films such as “Some Like It Hot” and “Gentlemen Prefer Blondes.”

According to a biography published in 1985, Monroe’s endometriosis was so severe that it destroyed her marriages, her wish for children, her career and ultimately her life.

The Endometriosis Collective said the documentary shares newly uncovered information about Monroe’s experience with endometriosis.

The non-profit said the information connects Monroe’s story to the experiences of women across generations, highlighting how far awareness, research and care still have to go.

A representative of the Marilyn Monroe Estate said: “By sharing this part of her story through ‘End of the Cycle,’ we hope to honour her legacy in a way that brings visibility to endometriosis, encourages more open dialogue and helps inspire the research needed to create change.”

As part of the premiere, The Endometriosis Collective is holding a panel discussion.

Schumer, Brown and Olowofoyeku, the documentary’s co-directors Sammy Jaye and Soraya Simi, and medical experts are due to be part of the premiere.

AbbVie’s Orilissa and Sumitomo Pharma’s Myfembree are among the approved drugs for endometriosis pain.

Hough, one of the participants in the documentary, starred in an Orilissa campaign in 2017.

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