KEY TAKEAWAYS
- The study aimed to investigate the impact of TRF2-mediated autophagy regulation on tumor sensitivity to taxane-based therapy in TNBC patients.
- Researchers noticed that TRF2, implicated in tumor development, could be a potential biomarker for predicting taxane-based neoadjuvant chemotherapy response in TNBC patients.
Breast cancer (BC) exhibits significant heterogeneity, leading to distinct prognoses and clinical management strategies. Triple-negative breast cancer (TNBC), known for its aggressive nature, remains resistant to many therapies, emphasizing the continued reliance on taxane-based treatment.
Despite this, the variability in TNBC patient responses underscores the urgent need for more effective management approaches. Telomeric Binding Factor 2 (TRF2), an overexpressed regulator of telomere integrity in TNBC and various tumors, has recently been implicated in autophagy modulation, a process crucial for drug detoxification.
Sara Iachettini and the team aimed to investigate the potential impact of TRF2-mediated autophagy regulation on TNBC’s sensitivity to therapy.
They performed an inclusive analysis on human TNBC cell lines, differentially expressing TRF2, to examine the impact of TRF2 on taxane treatment efficacy. Cell lines underwent treatment with various taxanes, evaluating autophagic response and cell proliferation. Biochemical assessment of autophagy involved measuring LC3 levels, while immunofluorescence analysis targeted LC3-puncta-positive cells.
Proliferation was assessed through colony formation assays, complemented by western blot and FACS analyses. Results were corroborated in mouse models, establishing the translational significance. Furthermore, the clinical relevance was underscored through a retrospective analysis of TNBC patients who underwent taxane-based neoadjuvant chemotherapy.
The study’s results identified an inhibitory role of TRF2 in autophagy, leading to heightened sensitivity of TNBC cells to taxanes. Initial observations in in vitro models were consistently replicated in preclinical mouse models.
Crucially, these findings were further validated in a TNBC patient cohort, conclusively establishing that TRF2 over-expression significantly amplifies the effectiveness of taxane-based neoadjuvant therapy. This enhanced efficacy substantially reduces tumor growth and decreases recurrence following surgical intervention.
The study concluded that TRF2 acknowledged for its involvement in tumor promotion and progression, emerges as a potential vulnerability in cancer. In this context, TRF2 holds promise as a prospective biomarker for anticipating the response of TNBC patients to taxane-based neoadjuvant chemotherapy.
The study is sponsored by Ministero della Salute and Associazione Italiana per la Ricerca sul Cancro
Source: https://pubmed.ncbi.nlm.nih.gov/38459559/
Iachettini S, Terrenato I, Porru M, et al. (2024). TRF2 as novel marker of tumor response to taxane-based therapy: from mechanistic insight to clinical implication. J Exp Clin Cancer Res. 2024 Mar 9;43(1):75. doi: 10.1186/s13046-024-02998-w. PMID: 38459559; PMCID: PMC10924347.
