For some men with advanced prostate cancer, chemotherapy initially appears to keep the disease at bay and then tests reveal that metastases are progressing. Doctors then speak of resistance, a phenomenon that is still difficult to predict.
A study from Weill Cornell Medicine, published in 2026 in the journal Nature Communicationsinvolves a gene,
FOXJ1. This gene appears to promote resistance to chemotherapy by taxaneswhose
docetaxelstandard treatment for metastatic prostate cancer.
When taxanes stop working in prostate cancer
THE
docetaxela taxane, is the first-line chemotherapy for metastatic prostate cancer and the only one to have shown an improvement in survival. However, many tumors end up escaping treatment, without us knowing in advance which patients will be affected.
To understand this problem, researchers developed xenografts of patient tumors in mice, treated with repeated cycles of docetaxel until resistance appeared. In these tumors that have become refractory, the activity of the gene
FOXJ1 and several genes related to microtubules – internal rails that help cells divide – was markedly increased.
FOXJ1, the gene that disrupts the “rails” targeted by docetaxel
Taxanes attach to these microtubules and stabilize them, blocking tumor cell division, but when the researchers artificially increased FOXJ1 in prostate cancer cells, they became less sensitive to docetaxel, whereas by decreasing its expression they became vulnerable again. “This role of the FOXJ1 transcription factor was previously unknown and could constitute a potential biomarker to identify patients likely to respond better to these treatments.“, said Dr. Paraskevi Giannakakou, professor of pharmacology in medicine, as quoted by Weill Cornell Medicine. “Additionally, this work paves the way for the development of future therapies capable of blocking this resistance pathway and restoring drug efficacy.”
“These results are exciting because they identify a role for FOXJ1 in controlling microtubule behavior in cells lacking cilia and show that tumor cells can exploit this function to develop resistance to taxanes.“, explained Dr. Steven Balk, professor of medicine at Harvard Medical School and oncologist at Beth Israel Deaconess Medical Center, who co-led this work.
Towards a future biomarker to personalize chemotherapy
By analyzing patient tumors, the researchers saw that the FOXJ1 gene was more often amplified after treatment with taxanes, and that high levels before treatment, in the CHAARTED trial combining docetaxel and hormone therapy, went hand in hand with shorter survival. “It was clear that patients who overexpressed FOXJ1 did not benefit as much from taxane therapy“, said Dr. Giannakakou.
FOXJ1 therefore appears as a possible predictive biomarkerto be validated before routine use. “We are optimistic that these findings will allow us to improve taxane-based therapies in prostate cancer and other cancers where taxanes are used.” said Dr. Balk.