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.”

Agilent has FDA approval for a test to identify ovarian cancer patients who may be eligible for immunotherapy.

Agilent’s PD-L1 IHC 22C3 pharmDx is the only FDA-approved companion diagnostic to help identify patients with epithelial ovarian, fallopian tube or primary peritoneal carcinoma whose tumours express PD-L1 and who may be eligible for treatment with KEYTRUDA, Merck’s anti-PD-1 therapy.

A companion diagnostic is a test used alongside a specific treatment to show whether a patient is suitable for that therapy. PD-L1 is a protein on some cancer cells that helps tumours evade the immune system.

These cancers affect the reproductive system and the lining of the abdominal cavity.

The test enables pathologists to assess PD-L1 expression at diagnosis to support treatment decisions in a disease where options remain limited for many.

This is the seventh FDA-approved companion diagnostic indication for PD-L1 IHC 22C3 pharmDx for use with KEYTRUDA.

Nina Green, vice president and general manager of Agilent’s clinical diagnostics division, said: “Delivering effective precision oncology requires close collaboration between diagnostics and therapeutics, and this FDA approval reflects Agilent’s long-standing industry partnership in companion diagnostics.

“We are proud to enable pathologists to identify patients with EOC who may benefit from immunotherapy.

“As the first immuno-oncology approval for this disease, this milestone underscores our commitment to advancing precision medicine and expanding access to innovative cancer treatments worldwide.”

PD-L1 expression with this test was evaluated in the KEYNOTE-B96 clinical trial supporting its use to identify patients who may benefit from KEYTRUDA.

In the US, ovarian cancer caused approximately 12,730 deaths in 2025 and the five-year survival rate was 51.6 per cent between 2015 and 2021.

In addition to these cancer types, the test is indicated in the US to help identify patients with non-small cell lung cancer, oesophageal squamous cell carcinoma, cervical cancer, head and neck squamous cell carcinoma, triple-negative breast cancer and gastric or gastro-oesophageal junction adenocarcinoma who may benefit from treatment with KEYTRUDA.

The test was developed by Agilent with Merck as a companion diagnostic for KEYTRUDA.

Breakthroughs in cancer care don’t only come from large institutions or fully funded labs.

They also come from determined individuals, small teams, early-stage founders, clinicians with an idea, researchers testing a new approach, technologists building smarter tools and advocates redesigning how care is delivered.

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