2023-04-22 01:36:28
Brain metastases are among the most feared complications of advanced cancer. Scientists in Vienna have now identified a possible target for new therapies: so-called HER3 receptors in breast cancer and non-small cell lung cancer.
The corresponding scientific work was published a few days ago in Clinical Cancer Research (doi: 10.1158/1078-0432.CCR-23-0020). Erwin Tomasich (MedUni Vienna) and the mostly Vienna team of authors with the head of the Clinical Division for Oncology, Matthias Preusser and Anna Berghoff (Internal Neuro-Oncology/MedUni Vienna): “There is still an enormous need for options for drug treatment of patients with Brain metastases. We therefore investigated whether the expression of HER3 (a receptor for kinase enzymes that drive cell growth; NB) could serve as a basis for future clinical trials in brain metastases from breast cancer and non-small cell lung cancer.”
Enhanced growth
HER3 can be formed on the surface of malignant cells. Similar to HER2, these are receptors for certain growth factors. Cancer cells produce these factors and often also develop (express; note) more receptors for these proteins on their surface. This leads to increased growth and increased cell division, which accounts for the selective advantage of cancer cells over benign cells.
The team of scientists analyzed tissue samples from 180 brain metastases from breast and lung cancer and 47 metastases from non-small cell lung cancer outside the brain. They also determined the density of immigrated immune cells in the malignant tissue.
The scientists’ results speak in favor of HER3 as a possible target for future drug therapies. “99 of 132 (75 percent) of brain metastases in breast cancer and 35 of 48 brain metastases in non-small cell lung cancer (72.9 percent) expressed HER3.” Brain metastases in HER2-positive breast cancer (15 to 20 percent of breast cancers) also showed more HER3 receptors on their surface (87.7 percent compared to 61 percent in HER2-negative breast cancer).
future therapies
The cell characteristic HER3 was found significantly more often in brain metastases as a result of lung carcinoma than in metastases outside the brain (72.9 versus 41.3 percent). HER3 apparently had no effect on the density of immune cells that had migrated into tumor tissue. HER3 also did not change the survival rate of the patients.
However, according to the authors, the results of this study could open up possibilities for future therapies. The HER2 receptor, which is related to HER3, has been used for around 20 years as a targeted target for monoclonal antibodies (trastuzumab) and for years also for trastuzumab-chemotherapy combinations (conjugates). This has made HER2-positive tumors much more treatable.
The scientists’ idea: One could also couple chemotherapy agents to monoclonal antibodies against HER3. The monoclonal antibodies would target the malignant cells of brain metastases and unload the chemotherapy agents there. In the case of HER2-positive tumours, this has worked for many years and has led, among other things, to the fact that the HER2-positive form of breast cancer, which was once considered to be particularly aggressive, has lost some of its terror.
medication
“Given the promising effects of antibody-drug conjugates in tumors metastatic outside the skull, it would be time to develop and test potential drugs that target brain metastases with HER3,” the researchers wrote. Preusser told the APA: “Such antibody-drug conjugates against HER3 are in clinical development and we are currently working at full speed on a clinical study specifically for patients with brain involvement in breast and lung cancer.”
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