UT Health San Antonio scientists have discovered that non-hydrolysable forms of ATP reduce cell migration and proliferation in metastatic cancers.
Background:
ATP (adenosine 5'-triphosphate) has been proposed as a therapeutic agent to improve nutritional status, reduce fatigue, reduce side effects associated with chemotherapy, and promote overall quality of life for patients suffering from cancer. ATP has also been shown to have anti-neoplastic activity, inhibiting growth in several cancer cell models by binding extracellular purinergic receptors. However, adenosine, the product resulting from degradation hydrolysis of ATP, promotes cancer cell proliferation, migration and potential for metastasis. Therefore, use of ATP therapy may pose a potential risk for cancer patients.
UT Health scientists have demonstrated that non-hydrolysable forms of ATP reduced cell migration and proliferation in a dose-dependent manner when tested with metastatic cancer cells, including breast cancer and prostate cancer models. The scientists have also demonstrated that adenosine receptor antagonists effectively block the stimulatory effect of adenosine on human breast cancer cells. Ongoing studies are exploring use of non-hydrolysable ATP, or in combination with adenosine receptor antagonists to reduce cancer growth, migration and metastasis.
In vitro studies and mouse xenograft and syngeneic models have demonstrated the following:
- ATP and adenosine have a stimulatory effect on human breast cancer cells and this effect is blocked by an adenosine receptor antagonist
- Non-hydrolysable ATP analog inhibits human breast cancer cell growth and migration
- Non-hydrolysable ATP analog inhibits, while adenosine promotes human breast cancer cell growth in a xenograft model in immuno-compromised mice
- Non-hydrolysable ATP analog inhibits bone metastasis of breast cancer cells in a syngeneic mouse model
Commercial Applications and Benefits:
This discovery has wide-ranging applications in the field of oncology and provides advantages over the current standard of care in the following ways:
- Non-hydrolysable ATP may provide a useful approach to treat primary cancer and reduce the potential for metastasis
- Performance may be improved when combined with an adenosine receptor antagonist