The following is a summary of “PLK4 as a potential target to enhance radiosensitivity in triple-negative breast cancer,” published in the February 2024 issue of Oncology by Pellizzari et al.

Resistance to radiotherapy poses a significant challenge in treating triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer. Previous studies have demonstrated that inhibiting Polo-like Kinase 4 (PLK4) with the novel drug CFI-400945 enhances the efficacy of radiotherapy (RT) in TNBC. Here, the researchers delve deeper into the role of PLK4 in augmenting radiation effects in TNBC and investigate the mechanisms underlying the combined antiproliferative effects of PLK4 inhibition and radiation. 

Colony formation assays in TNBC cell lines and patient-derived organoids (PDOs) were employed to evaluate cellular proliferation in response to treatments. PLK4 expression was downregulated using siRNA silencing in TNBC cell lines, and immunofluorescence against centrin was utilized to assess centriole amplification alterations. Their findings reveal that inhibiting PLK4 with CFI-400945 or Centrinone B or silencing its expression with siRNA, in combination with RT, significantly enhances the antiproliferative effects in TNBC cell lines and PDOs compared to single or untreated cells. Synergistic anticancer effects were observed in PDOs treated with CFI-400945 and RT, as indicated by a response matrix analysis. The study group also observed that overamplification of centrioles may contribute to the combined antiproliferative action of RT and PLK4 inhibition. 

These results underscore the potential of PLK4 as a promising target for augmenting the anticancer effects of RT in TNBC, possibly mediated by centriole overamplification. This study highlights the importance of further investigating the mechanistic and translational aspects of anti-PLK4 agents combined with RT as a viable anticancer treatment strategy for TNBC.

Source: ro-journal.biomedcentral.com/articles/10.1186/s13014-024-02410-z