News
New drugs identified in hunt for aggressive breast cancer treatments
The search for more effective treatments for deadly metaplastic breast cancer has uncovered two drugs with the potential to interrupt disease progression.
US researchers examined the biology of metaplastic breast cancer, comparing it to non-metaplastic triple negative breast cancer.
They discovered metaplastic breast cancers typically exhibit two unique signaling pathways in their cell interaction.
Researchers were able to disrupt these pathways using a class of inhibitors typically used to treat advanced cancers – phosphoinositide 3 kinase inhibitor (P13K) – in combination with a nitric oxide inhibitor (NOS) typically used to treat septic shock, cardiovascular disease and other conditions.
When introduced to the cell, these drugs disrupted these pathways, making the treatment more effective.
Metaplastic breast cancer is a rare and aggressive form of disease and typically grows faster and is more likely to metastasise or spread to other parts of the body than other breast cancers.
It is also more likely to recur after successful initial treatment. Patients with metaplastic breast cancer will often receive the same treatment as a patient with triple negative breast cancer, another aggressive and deadly form of the disease. However, metaplastic breast cancer often does not respond well.
The study was led by Dr Jenny Chang, chief academic officer at the Houston Methodist Academic Institute.
She said: “This is a significant finding because it offers a promising therapeutic option for one of the most aggressive and difficult-to-treat subtypes of breast cancer.
“We have the potential to improve outcomes for patients who currently face limited treatment options and poor prognoses, marking an important step forward in cancer research and therapy.”
The first author, Dr Tejaswini Reddy added: “Our findings highlight a promising therapeutic combination that could hopefully change the landscape of metaplastic breast cancer treatment. Translating this research into a clinical trial is crucial to improving outcomes for patients facing this rare and aggressive disease. Moreover, this approach may have broader implications, potentially benefiting patients with other cancers with similar biology,” said Reddy.”
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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