lowering the levels of 53BP1 allows BRCA1 deficient cells to thrive and do their worst, increasing the levels of the protein offers a promising strategy for treatment of breast tumors.
In previous research, Gonzaloís team showed that vitamin D inhibits CTSL-mediated degradation of 53BP1 in non-tumor cells, as efficiently as specific CTSL inhibitors. This time, they found that treatment of BRCA1-deficient tumor cells with vitamin D restores high levels of 53BP1, which results in increased genomic instability and reduced proliferation.
Importantly, their evidence suggests that vitamin D treatment might restore the sensitivity to PARP inhibitors in patients who become resistant. Thus, a combination of vitamin D and PARP inhibitors could represent a novel therapeutic strategy for breast cancers with poor prognosis.
In a final exceptionally useful discovery, Gonzalo and collaborators found that high levels of nuclear CTSL and low levels of 53BP1 and nuclear vitamin D receptor (VDR) are a clear marker that identifies certain triple-negative breast cancer patients, biomarkers that offer the potential to customize future breast cancer therapies.
In particular, this triple-biomarker signature will allow the identification of patients in whom the pathway is on and who might benefit the most from vitamin D treatment.
The research was published recently in The Journal of Cell Biology.