Novel compounds have been developed based upon the capsazepine pharmacophore that are effective in halting tumor cell proliferation in vitro and in vivo. Capsazepine is a known, off-patent, analog of Capsaicin that has been proposed and studied as a TRPV1 antagonist for treatment of pain. Although Capsazepine has been proposed for alleviation of pain, previous studies have not identified Capsazepine as an effective anti-tumor agent.
Background:
Often, patients with head and neck cancers are inoperable because these tumors invade or are close to critical structures, such as the carotid artery, that may lead to fatal complications. Advanced oral cancer has a 70% death rate and there are no drugs available that effectively alleviate the pain associated with inoperable oral cancer.
The researchers have generated several analogs with anti-tumor effects, with 2 showing significant anti-tumor activity when tested in vivo. Data gathered from the development of these novel compounds demonstrates anti-tumor activity against oral cancers, primary breast cancer, and prostate cancer in vitro and oral cancer in vivo. Furthermore, efficacy studies in vivo revealed enhanced anti-tumor activity compared to the parent compound capsazepine. Testing showed as much as 80% reduction in human oral squamous cell carcinoma (OSCC) tumor growth in ten days without observable side effects. In contrast, capsazepine show only a 50% reduction in tumor growth under the same conditions. Also, administering capsazepine analogs by direct injection into solid tumors results in the reduction of tumor volume and may prevent tumor invasion of nerve bundles and the carotid artery. The novel capsazepine analogs have shown to lead to cellular apoptosis and can potentially be used to treat cancers such as an oral tumor, a tumor of the head and neck, primary breast cancer, cervical cancer, or prostate cancer.
Commercial Applications and Advantages:
These novel anti-tumor compounds have potential applicability for all solid tumors and provide the following benefits to the current standard of care:
• Induces significant tumor reduction by 80%
• Cause cellular apoptosis via reactive oxygen species (ROS) production
• Dramatically reduces tumor growth in oral cancer xenografts
• Alleviates pain by blocking TRPV1 channels present in pain sensing neurons
• Effective in multiple cancers, including breast and prostate cancer
• May prove useful for pain relief in palliative care