News
Boston start-up welcomes validation of tumour gangliosides as diagnostic markers for ovarian cancer detection
The results will be presented at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting
The US biotech company AOA Dx has announced the initial validation of GD2 and GD3 tumour marker gangliosides as novel diagnostic markers for early detection of ovarian cancer.
The start-up has developed a “novel” approach to evaluate tumour marker gangliosides in liquid biopsies for early cancer detection and develop new diagnostic tests.
Its AKRIVIS GD test detected ovarian cancer in all subtypes and stages, including stage I and II – the most challenging stages to diagnose.
According to the company’s data, it achieved an AUC of 0.969 for detection of ovarian cancer in early stages – a significant improvement over the standard of care.
Ovarian cancer is the deadliest gynaecological disease. Up to 95 per cent of women with ovarian cancer have symptoms for many months and consult a doctor, but the average time to diagnosis is nine months.
Detection of ovarian cancer at early-stages has a five-year survival rate of greater than 90 per cent, but when diagnosed at advanced stages, the five-year survival rate is less than 30 per cent.
“Today, ovarian cancer takes the lives of far too many women. The challenge of early diagnosis has been one that many have tried to tackle, but until today, we haven’t seen anything with the potential to catch the disease in early stages,” said Oriana Papin-Zoghbi, CEO and co-founder of AOA Dx.
“Our initial validation of AKRIVIS GD shows promising results, and an exciting first step towards improving the early detection of ovarian cancer.”
Professor Uri Saragovi, principal investigator, said: “Our research on tumour marker gangliosides over the past years has shown their potential as top targets for early detection of cancer.
“In our latest research, we were able to correctly identify disease in over 90 per cent of early stage subjects.”
The developers say AKRIVIS GD may enable detection of malignancy helping expedite workup and treatment plans and its validation could alleviate costs and increase survival rates.
The news of the initial validation comes weeks after the start-up announced a US$7m funding round to bring to market its first diagnostic test.
Diagnosis
Lung cancer drug shows breast cancer potential
Ovarian cancer cells quickly activate survival responses after PARP inhibitor treatment, and a lung cancer drug could help block this, research suggests.
PARP inhibitors are a common treatment for ovarian cancer, particularly in tumours with faulty DNA repair. They stop cancer cells fixing DNA damage, which leads to cell death, but many tumours later stop responding.
Researchers identified a way cancer cells may survive PARP inhibitor treatment from the outset, pointing to a potential way to block that response. A Mayo Clinic team found ovarian cancer cells rapidly switch on a pro-survival programme after exposure to PARP inhibitors. A key driver is FRA1, a transcription factor (a protein that turns genes on and off) that helps cancer cells adapt and avoid death.
The team then tested whether brigatinib, a drug approved for certain lung cancers, could block this response and boost the effect of PARP inhibitors. Brigatinib was chosen because it inhibits multiple signalling pathways involved in cancer cell survival.
In laboratory studies, combining brigatinib with a PARP inhibitor was more effective than either treatment alone. Notably, the effect was seen in cancer cells but not normal cells, suggesting a more targeted approach.
Brigatinib also appeared to act in an unexpected way. Rather than working through the usual DNA repair routes, it shut down two signalling molecules, FAK and EPHA2, that aggressive ovarian cancer cells rely on. FAK and EPHA2 are proteins that relay survival signals inside cells. Blocking both at once weakened the cells’ ability to adapt and resist treatment, making them more vulnerable to PARP inhibitors.
Tumours with higher levels of FAK and EPHA2 responded better to the drug combination. Other data link high levels of these molecules to more aggressive disease, pointing to potential benefit in harder-to-treat cases.
Arun Kanakkanthara, an oncology investigator at Mayo Clinic and a senior author of the study, said: “This work shows that drug resistance does not always emerge slowly over time; cancer cells can activate survival programmes very early after treatment begins.”
John Weroha, a medical oncologist at Mayo Clinic and a senior author of the study, said: “From a clinical perspective, resistance remains one of the biggest challenges in treating ovarian cancer. By combining mechanistic insights from Dr Kanakkanthara’s laboratory with my clinical experience, this preclinical work supports the strategy of targeting resistance early, before it has a chance to take hold. This strategy could improve patient outcomes.”
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