New biomarker of breast and prostate cancers holds promise for customizing treatment

Researchers have discovered a novel genetic biomarker—diaphanous-related formin-3, or DIAPH3—that is responsible for the progression of many breast and prostate cancers. This finding could help clinicians to identify patients who will respond better to common chemotherapy drugs. The study was published July 16, 2015, in Scientific Reports.

"Understanding and identifying biomarkers is a vital step toward cancer research and care," said lead author Michael Freeman, PhD, vice chair of research in the Cedars-Sinai Department of Surgery, in Los Angeles, CA. "New profiling strategies exemplified by this study will ultimately improve our ability to treat cancer patients."

The researchers found that when the DIAPH3 biomarker is lowered or lost, tumor cells take on a more aggressive, “amoeboid” phenotype. The cells lose rigidity in their microtubule (MT) cytoskeleton and become deformable, which allows them to squeeze through tissue spaces, cause disease progression or growth, and promote metastasis.

Ironically, the investigators found, DIAPH3 loss also alters MT stability and dynamics, which sensitizes cells to MT-directed chemotherapy—specifically the taxanes, such as paclitaxel and docetaxel. When DIAPH3 is silenced, the cytotoxic response to taxanes is increased in prostate and breast cancer cell lines, the researchers noted. This is the first study to identify a targeting strategy for tumor cells that exhibit amoeboid properties.

Clinicians could eventually use this knowledge to identify patients who will respond better to these therapies. “Our present findings suggest that profiling of tumors for DIAPH3 loss and related network perturbations, including levels of Ac-tubulin, may have predictive value in selecting rational treatment strategies for aggressive disease,” the researchers wrote.

“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, senior vice president of Academic Affairs and director of the Burns and Allen Research Institute at Cedars-Sinai. "This customized plan replaces a one-size-fits-all approach to cancer treatment."

The next step for the researchers will be to develop a biomarker tool to prospectively test these findings in patients.