TTUHSC Research Explores TBX2's Role in Prostate Cancer Bone Metastasis

Researchers at the Texas Tech University Health Sciences Center (TTUHSC) are embarking on a critical investigation into the role of TBX2, a transcription factor, in the bone metastasis of prostate cancer. This research is particularly significant as the American Cancer Society predicts that in 2025, more than 313,780 new cases of prostate cancer will be diagnosed in the United States, leading to an estimated 35,770 deaths. Bone metastasis, which occurs when cancer spreads to the bones, is the leading cause of prostate cancer-related mortality, complicating treatment options and severely impacting patient quality of life.

Dr. Srinivas Nandana, leading the study, is funded by a $1.85 million grant from the U.S. Department of Defense. His research focuses on understanding how TBX2 influences the establishment of the prostate cancer pre-metastatic niche in bone, a crucial step in the metastasis process. "Bone metastasis severely impacts patients, often leading to debilitating pain and functional impairments," Dr. Nandana emphasized. Current treatments for this advanced stage of prostate cancer primarily involve palliative care, with no effective strategy to halt disease progression.

The study builds on earlier findings published in the journal Cancer Research, which suggested that targeting the TBX2-WNT signaling axis could be a viable therapeutic strategy. The researchers propose that TBX2 facilitates the release of exosomes—tiny membrane-bound structures from cancer cells—into the bloodstream. These exosomes interact with normal bone cells, modifying them to create a conducive environment for metastatic growth.

Dr. Manisha Tripathi, co-investigator and an expert in cell biology and biochemistry, noted that their research aims to dissect the molecular pathways involved in this process. "We believe the TBX2-NOTCH axis is vital in preparing the bone microenvironment for cancer cell colonization," Dr. Tripathi stated. By employing laboratory models and genetic techniques, the team will explore the role of the NOTCH intracellular domain 3 (NICD3) protein in the bone metastasis pathway.

If successful, this research could pave the way for new therapeutic approaches to mitigate the risk of bone metastasis in prostate cancer patients. The team plans to examine the efficacy of gamma secretase inhibitors (GSIs), a class of anticancer drugs, in reducing NICD3 levels in tumor cells, thereby potentially impeding the metastatic process. Dr. Nandana remarked, "If we can disrupt this pathway, we hope to significantly lessen the ability of prostate cancer to spread to the bone."

The implications of this research extend beyond patient prognosis; they may also lead to the repurposing of existing medications for prostate cancer treatment, expediting the availability of new therapies. "Understanding early-stage interactions between cancer cells and bone could revolutionize our approach to treating advanced prostate cancer," Dr. Nandana concluded. As the study progresses, it promises to offer vital insights into the mechanisms of prostate cancer metastasis, potentially improving quality of life and outcomes for affected patients.