Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer that lacks estrogen receptor (ER), progesterone receptor (PR), and HER2, but about 10–43% of TNBCs still express the androgen receptor (AR). Those that don’t are called “quadruple-negative” or AR-negative TNBC (AR TNBC). These cancers tend to be more aggressive, harder to treat, and carry poorer prognoses, mainly because usual hormone therapies aren’t effective.

The study “C/EBPβ increases tumor aggressiveness by enhancing KIFC1 expression in androgen receptor negative triple negative breast cancer” explores whether two proteins— CCAAT/enhancer binding protein beta (C/EBPβ, a gene-regulating protein) and kinesin-like protein 1 (KIFC1, a motor protein crucial in cell division)—play a key role in AR TNBC. Understanding their interactions could point to new therapeutic targets. This research has several implications, including:

• This research uncovers the AR → C/EBPβ → KIFC1 pathway as a key driver of AR-negative TNBC aggressiveness.
• Since KIFC1 is less important for normal cells but vital for cancer cell survival and spread, it presents an attractive drug target.
• Inhibitors like CW069 may offer a promising new treatment for patients with AR-negative TNBC, pending further clinical validation.

In conclusion, the study reveals how loss of AR leads to increased C/EBPβ, which drives KIFC1 up, fueling cancer growth and spread in AR-negative TNBC. Blocking KIFC1 effectively slows tumor progression both in cells and in mice, opening the door to a novel targeted therapy for this challenging cancer subtype.

Reference: Joshi S, Garlapati C, Nguyen T, et al. C/EBPβ increases tumor aggressiveness by enhancing KIFC1 expression in androgen receptor negative triple negative breast cancer. Cell Commun Signal 23, 255 (2025). https://doi.org/10.1186/s12964-025-02243-7.