KEY TAKEAWAYS
- The study aimed to determine the efficacy of new EGFR inhibitors in targeting breast CSCs and increasing chemotherapeutic sensitization to improve TNBC treatment outcomes.
- Researchers noticed that blocking EGFR makes aggressive breast CSCs in TNBCs more responsive to chemotherapy, potentially lowering cancer relapse.
Metastasis is a particular challenge in triple breast cancer (TNBC) with frequent poor prognosis and disease recurrence. Central to TNBC metastasis are breast cancer stem cells (CSCs) are involved in tumorigenesis and treatment resistance.
Trisha Kar and her team aimed to evaluate the epidermal growth factor receptor (EGFR), which is overexpressed in breast CSCs and represents a prospective therapeutic target for TNBC treatment. As a result, there is an urgent need for effective EGFR inhibitors that can disrupt downstream signaling pathways linked with breast cancer proliferation and tumorigenesis.
To find small molecule EGFR inhibitors, the researchers performed an inclusive analysis and molecular docking experiments. Following in-vitro screening of the compounds, cytotoxicity profiles were determined, and non-cytotoxic compounds’ effects on doxorubicin-induced migration, in-vitro tumorigenesis potential, and modulation of pro-apoptotic gene and protein expression in TNBC cells were assessed.
Compound 1e demonstrated particularly promising results, increasing doxorubicin’s inhibitory effects on proliferation, migration, in-vitro tumorigenesis, and apoptosis induction in MDA-MB-231 cells, as well as in sorted CD24+-breast cancer cells and CD24-/CD44+-breast CSC populations. Furthermore, molecular and immunohistochemical studies revealed that low-dose doxorubicin effectively prevented orthotopic xenotransplantation of breast CSC-induced tumors in C57BL/6J mice.
The study concluded that EGFR inhibition-mediated sensitization of aggressive and metastatic breast CSCs in TNBCs toward chemotherapeutics holds promise for reducing disease relapse.
Source: https://pubmed.ncbi.nlm.nih.gov/38522013/
Kar T, Dugam P, Shivhare S, et al. (2024). “Epidermal growth factor receptor inhibition potentiates chemotherapeutics-mediated sensitization of metastatic breast cancer stem cells.” Cancer Rep (Hoboken). 2024 Mar;7(3):e2049. doi: 10.1002/cnr2.2049. PMID: 38522013; PMCID: PMC10961089.
