DIAPH3 silencing reduces the population of stable MT and alters MT topology. NB. Inhibition of MT stability arising from DIAPH3 downregulation enhances susceptibility to MT poisons, and that the DIAPH3 network potentially reports taxane sensitivity in human
The biomarker – diaphanous-related formin-3 or DIAPH3 – participates in a protein interaction that makes cells rigid. The study found that when this biomarker is lost or lowered, cells become “deformable,” squeezing through tissue spaces, causing disease growth or progression. This phenomenon is known as an amoeboid phenotype.
ie DIAPH3 interacted with microtubules (MT), and its loss altered several parameters of MT dynamics as well as decreased polarized force generation, contractility, and response to substrate stiffness. Silencing of DIAPH3 increased the cytotoxic response to taxanes in prostate and breast cancer cell lines. Low DIAPH3 expression correlated with improved relapse-free survival in breast cancer patients treated with chemotherapeutic regimens containing taxanes
Researchers can utilize this knowledge to better identify patients who will respond to common chemotherapy drugs, called taxanes, which are typically given to patients with the most aggressive forms of cancer. Taxanes work by damaging protein structures in cancer cells.
This is the first study to identify a targeting strategy for tumor cells that exhibit amoeboid properties. “By identifying cancer biomarkers, then customizing treatment plans for individuals based on this genetic information, we can greatly improve the effectiveness of cancer therapies,” said Shlomo Melmed, MD,..”This customized plan replaces a one-size-fits-all approach to cancer treatment.”
Next steps involve the development of a biomarker tool that will allow researchers to test these findings prospectively in patients. http://www.cedars-sinai.edu/About-Us/News/News-Releases-2015/New-Biomarker-Identified-in-Breast-and-Prostate-Cancers-Holds-Promise-for-Treating-Disease.aspx
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