TTUHSC researchers seek to understand the role of TBX2 in bone metastasis of prostate cancer

The American Cancer Society estimates that more than 313,780 cases of prostate cancer will be diagnosed in the United States in 2025, resulting in approximately 35,770 deaths. Bone metastasis, a stage of prostate cancer where the disease spreads to the bones, is the main cause of death related to prostate cancer and currently remains incurable.

This stage of prostate cancer is devastating for the patient, since it often affects the bones of the spine, resulting in severe pain for fractures and compression of the spinal cord, together with significant neurological and functional disabilities. The current treatment for this advanced stage of the disease is limited to palliative care aimed at relieving symptoms, without any real hope of reducing or limiting the progression of the disease itself. “

Srinivas Nandana, Ph.D., Ttuhsc

With the support of a three-year subsidy and $ 1.85 million from the United States Department of Defense (“” TBX2 in the establishment of the metal niche of prostate cancer (PMN) in the bone “), Nandana and Co-Investigator Manisha Tripathi, Ph.D. of the Department of Biogology of Cellular and Biochemistry in the Texas Texas Texas Texas Texas Tex Scianses (Ttuhcet Tuhcec).

The Nandana Laboratory has focused on deciphering the role of TBX2 in prostate cancer for more than a decade, mainly supported by DOD subsidies, the Texas-Texas Cancer Cancer Research Institute Regional Excellence in Cancer, the Ted Nash Long Life Foundation and the CH Foundation. Based on the findings of his previous study published in Cancer Research (“Bone metastasis of prostate cancer can be therapeutically directed in the TBX2-WNT signaling axis) and the new data, Nandana and tripathi will investigate the first stages of the bone metastasis process.

During these stages, the primary prostate tumor continually releases the small sack -type membrane structures called exosomes, which contain proteins and RNA molecules. These exosomes travel through the bloodstream and interact with normal bone cells. Once in the bone, they share their molecular contents, which makes bone cells “remodellen” in a potential site of future “nesting” or “pretmethassical niche”, which makes the bone more hospitable for the cancer cells that arrive.

At some point, said Nandana, a circulating cancer cell house in one of these bone nesting sites and then grows, divides and becomes a new metastatic tumor mass.

“We believe that a specific molecular route, the TBX2 notch axis, plays a key role in the preparation of bones to house these cancer cells,” Nandana explained. “Our goal is to test ways of blocking or interrupting this route. In doing so, we hope to reduce significantly, or even prevent, the capacity of prostate cancer to spread to the bones. We also believe that, driven by the signage of TBX2, the exosomal transport of the intracellular domain of notch mastery 3 (NICD3) to the bone cells to the bone cells in all the bone remodeling of the bone remodeling of the notice of the bone remodeling of the notice.

Nandana said that a more complete understanding of this early mediated communication system of exosomes between the primary prostate tumor and the bone can open new ways to intervene and interrupt the process, potentially slowing down or even anticipating bone metastases.

In their next studies, Nandana and Tripathi will combine the use of laboratory models and human prostate cancer mice with genetic techniques to study NICD3 protein. Its objective is to determine if the NICD3 protein, secreted in exosomes due to high TBX2 in tumor cells, is essential to create the bone environment that allows metastatic prostate cancer cells to establish and grow.

“We will also evaluate whether an existing class of anti -cancer drugs, known as Gamma Secretary inhibitors (GSI), can reduce the formation of NICD3 in primary tumor cells to insufficient levels to initiate bone remodeling and the metastatic process, thus reducing or potentially prevent bone metastases of prostate cancer,” said the nandana. “The GSI are clinically approved agents, so if they succeed, direct clinical tests could quickly proceed.”

If the investigation is successful, Nandana said that it could lead to new treatment approaches aimed at slowing or preventing bone metastasis of prostate cancer, a significant advance taking into account that bone metastases are currently incurable are already often in an intense pain, fractures and loss of mobility. Stop metastasis before it begins could significantly improve the results and quality of life of patients.

As part of the study, Nandana and Tripathi will also evaluate drugs already approved for other conditions. If any of these medications is promising, they could be reused for the treatment of prostate cancer faster than recently developed therapies.

“While this research is still in its early stages, it offers new promising ideas about how prostate cancer spreads and how we could intervene before in that process,” Nandana said. “Bone metastases causes serious problems for patients, including reduced pain and mobility. If we can better understand how cancer interacts with bone in the early stages, we could reduce the impact of advanced disease. This could help improve comfort and quality of life for some patients, and potentially delay or prevent complications related to bone metastases.”