News
Roche’s breast cancer companion diagnostic receives CE Mark
The companion diagnostic test could aid in the assessment of metastatic breast cancer patients who may be eligible for Enhertu
Roche has received the CE Mark for the first companion diagnostic test to identify patients with HER2-low metastatic breast cancer who may be eligible for Enhertu, a type of targeted cancer drug.
Enhertu (trastuzumab deruxtecan), jointly developed and commercialised by Daiichi Sankyo and AstraZeneca, is a HER2-directed antibody drug conjugate.
Roche’s Ventana HER2 (4B5) Rabbit Monoclonal Primary Antibody RxDx test is the first, and thus far only, companion diagnostic test approved to aid in the assessment of metastatic breast cancer patients who may be eligible for treatment with Enhertu, which could significantly improve their outcome.
The test, which is branded PATHWAY in the US, received US Food and Drug Administration (FDA) approval in October 2022.
HER2 is a receptor protein that helps cancer cells grow quickly. To determine a patient’s HER2 status, pathologists evaluate, or score, the level of HER2 protein expressed in breast cancer tissue samples.
If a patient’s tumour expresses high levels of HER2, the patient is identified as HER2-positive and may be considered for HER2-targeted treatment. However, half of all patients with metastatic breast cancer express low levels of HER2 which historically classified them as HER2-negative.
According to Roche, the VENTANA HER2 (4B5) test includes a scoring algorithm that helps pathologists to identify “low expressors” of HER2, assigning a HER2 low status to this group of patients. With this lower cutoff, the test could identify patients who may benefit from Enhertu as a treatment option.
Breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with more than two million new cases diagnosed worldwide each year. More than 685,000 people die from breast cancer every year.
Jill German, head of pathology lab at Roche Diagnostics, said: “We are proud to continue our innovation in breast cancer diagnostics through critical tests like this one, which helps identify patients with HER2-low status.
“With this expanded approval of our test, we’re pleased that more metastatic breast cancer patients across the world may be correctly identified and potentially eligible for this targeted therapy.”
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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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