This technology uses bethanechol to treat pancreatic cancer by reducing proliferation of pancreatic tumor cells, inhibiting pancreatic cancer metastasis, or inhibiting the growth of pancreatic cancer stem cells.
Unmet Need: Treatment for pancreatic cancer with reduced proliferation of tumor cells
Current treatments for pancreatic cancer rely on a combination of chemotherapy, surgery, and radiation to slow tumor growth or remove the affected cells. This often fails to improve long-term survival due to surrounding stroma that sustains the tumor. Certain patients, especially those with widespread disease or metastasis, often rely on chemotherapy and radiation as useful adjuvant treatments. However, pancreatic ductal adenocarcinoma (PDAC) is particularly resistant to treatment due to the tumor microenvironment and continues to have the lowest 5-year survival rate for cancers.
The Technology: Effective method to treat pancreatic cancer through cholinergic stimulation
This technology utilizes cholinergic agonists to activate the muscarinic-3 receptor (M3R) to modulate the proliferation of pancreatic tumor cells. Treatment with bethanechol, a broad cholinergic muscarinic receptor agonist, and other related cholinergic agents can suppress the growth of human pancreatic cancer cells primarily by suppressing pancreatic cancer stem cells. Cholinergic stimulation also reduces tumor infiltration by tumor-associated macrophages and stimulates normal pancreatic growth. Thus, bethanechol can be used as an effective medication with limited toxicity for advanced PDAC or PDAC metastases, or as neoadjuvant therapy.
This technology has been validated in mice treated with bethanechol and a variety of standard treatment options. Additionally, this technology has been used to significantly extend survival in mouse models of pancreatic cancer.
Applications:
- Treatment of GI tract inflammation disorders such as ulcerative colitis or radiation induced gastrointestinal symptoms
- Mitigation of intestinal colitis/proctitis caused by chemotherapy or radiation
- Treatment for pancreatic cancer
- Production of stem cells in GI tract
- Improving outcomes after intestinal surgery
- Treatment for liver metastases
Advantages:
- Stimulates body’s own stem cells to help repair damaged tissue
- Can be administered pre- or post- radiation treatment
- Treats an underlying condition, rather than just symptoms
- Uses an FDA-approved, well-tolerated drug
- Multiple formulations
Lead Inventor:
Timothy Wang, M.D.
Patent Information:
Patent Status
Related Publications:
Renz BW, Takahashi R, Tanaka T, Macchini M, Hayakawa Y, Dantes Z, Maurer HC, Chen X, Jiang Z, Westphalen CB, Ilmer M, Valenti G, Mohanta SK, Habenicht AJR, Middelhoff M, Chu T, Nagar K, Tailor Y, Casadei R, Di Marco M, Kleespies A, Friedman RA, Remotti H, Reichert M, Worthley DL, Neumann J, Werner J, Iuga AC, Olive KP, Wang TC. “β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic Cancer” Cancer Cell. 2018 Jan 8; 33(1): 75-90.
Renz BW, Tanaka T, Sunagawa M, Takahashi R, Jiang Z, Macchini M, Dantes Z, Valenti G, White RA, Middelhoff MA, Ilmer M, Oberstein PE, Angele MK, Deng H, Hayakawa Y, Westphalen CB, Werner J, Remotti H, Reichert M, Tailor YH, Nagar K, Friedman RA, Iuga AC, Olive KP, Wang TC. “Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness” Cancer Discov. 2018 Nov; 8(11): 1458-1473.
Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, Renz BW, Tailor Y, Macchini M, Middelhoff M, Jiang Z, Tanaka T, Dubeykovskaya ZA, Kim W, Chen X, Urbanska AM, Nagar K, Westphalen CB, Quante M, Lin CS, Gershon MD, Hara A, Zhao CM, Chen D, Worthley DL, Koike K, Wang TC. “Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling” Cancer Cell. 2017 Jan 9; 31(1): 21-34.
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