The American Cancer Society predicts that over 313,780 cases of prostate cancer will be diagnosed in the U.S. in 2025, leading to around 35,770 deaths. Bone metastasis, where the cancer spreads to the bones, is the primary cause of death related to prostate cancer and remains incurable.

This stage of prostate cancer is particularly devastating as it affects the spine bones, causing severe pain, fractures, spinal cord compression, and functional disabilities. Current treatments focus on symptom relief rather than disease progression.

With a $1.85 million grant from the U.S. Department of Defense, researchers Srinivas Nandana and Manisha Tripathi from Texas Tech University Health Sciences Center will study the role of TBX2, a transcription factor, in establishing the premetastatic niche in bone for prostate cancer. Their goal is to enhance understanding of prostate cancer metastasis and develop new treatment methods.

Nandana's lab has been investigating TBX2's role in prostate cancer for over a decade, supported by various grants. Building on previous findings, they aim to explore the early stages of bone metastasis.

During these stages, exosomes released by the primary prostate tumor interact with normal bone cells, preparing the bone for potential cancer cell nesting. The TBX2-NOTCH axis is believed to play a crucial role in this process, and disrupting this pathway could prevent or reduce bone metastasis.

The researchers will use laboratory and mouse models to study the NICD3 protein and evaluate the effectiveness of gamma secretase inhibitors in reducing NICD3 formation and preventing bone metastasis. If successful, this research could lead to new treatment strategies to slow or prevent prostate cancer bone metastasis.

Understanding how cancer interacts with bone in the early stages could improve patient outcomes and quality of life, potentially delaying or preventing complications related to bone metastases.